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1 Department of Physiology and Biophysics, University of Medicine & Dentistry of New Jersey-Robert Wood Johnson School of Medicine, Piscataway, NJ 08854, USA2 Department of Molecular Microbiology & Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA3 Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
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Abstract |
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50% in malarial muscles. In addition, the contractile proteins of Triton-skinned muscle fibres from malarial muscles were significantly less sensitive to Ca2+. Biochemical analysis revealed that there was a significant loss of essential contractile proteins (e.g. troponins and myosin) in Triton-skinned muscle fibres from malarial muscles as compared to controls. The biochemical alterations (i.e., reduction of essential contractile proteins) seem to explain well the functional modifications resolved in both intact muscles and Triton-skinned muscle fibres and may provide a suitable paradigm for the aetiology of muscle symptoms associated with malaria.
(Received 25 June 2004;
accepted after revision 14 February 2005; first published online 22 February 2005)
Corresponding author M. Brotto: Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson School of Medicine, Piscataway, NJ 08854, USA. Email: brottoma{at}umdnj.edu
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Introduction |
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The focus of our studies was to determine the functional and biochemical effects of malaria on the contractile apparatus. To achieve our aim, we studied the fast-twitch, glyoclytic extensor digitorium longus (EDL) muscle and the slow-twitch, oxidative Soleus (SOL) muscle from mice-infected with Plasmodium berghei with a parasitaemia level of 35%. We measured the maximal tetanic force produced by intact muscles before, during and after fatigue. Effects on intact muscles can result from a combination of events directly correlated with either the excitation–contraction coupling (e.g. sarcoplasmic reticulum (SR) Ca2+ release and Ca2+ uptake) or with the contractile proteins (e.g. changes in Ca2+ sensitivity, changes in maximal Ca2+-activated force). To conclusively demonstrate the effects of malaria infection at the contractile protein level, Triton-skinned muscle fibres were utilized to determine the isometric contractile properties of both EDL and SOL muscles as well as the basic biochemical features of these muscles analysed by silver-enhanced SDS-PAGE.
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Methods |
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Fourteen (7 control, 7 malarial) 8-week-old Swiss Webster male mice weighting 25–30 g (Harlan Laboratories, Indianapolis, IN, USA) were killed by CO2 inhalation. All procedures were performed in accordance with the Guiding Principles in the Care and Use of Animals approved by the American Physiological Society and the Animal Protocol Review Committee of the School of Medicine at Case Western Reserve University and University of Medicine & Dentistry of New Jersey.
Malarial infection
P. berghei ANKA-2.34 parasites, isolated from Thicket rats (Grammomys surdaster) have been maintained by passage through Swiss Webster mice in our laboratory as previously described (Hoffmann et al. 1984). For infection, mice were intravenously infected with identical frozen aliquots of erythrocytes infected with malaria parasites, by a bolus injection of 200 µl infected blood with 25% parasitaemia (diluted in PBS). Parasitaemia was monitored on a daily basis by microscopic analysis of blood smears stained with Giemsa. Mice with parasitaemia of 35% were selected for functional and biochemical assays because in a set of pilot studies they displayed a clear muscle-related phenotype (i.e. increased fatigability) without displaying any signs of brain dysfunction (i.e. deviation of the head, convulsion and coma followed by death). Thus, in our study, only mice without brain-related symptoms were used. These targeted levels of parasitaemia were achieved 3–6 days after the injection of the parasite. Control and malarial animals were matched for strain, age and weight.
Materials
Giemsa kits were from Gemco (Hudson, OH, USA). All other chemicals were of analytical grade (Sigma, St Louis, MO, USA).
Intact muscle preparation
These experiments were performed following the protocols established by Brotto et al. (2001, 2002). Animals were killed by CO2 inhalation and intact EDL and SOL muscles were removed and placed in a dissecting dish containing a modified Ringer solution having the following composition (mM): NaCl 136.5, KCl 5.0, CaCl21.8, NaH2PO4 0.4, MgCl2 0.5, NaHCO3 11.9 and glucose 10; pH 7.4, continuously bubbled with 95% O2–5% CO2 at 25 ± 1°C. Fetal calf serum (0.2%) was added to the solution to increase viability of the dissected muscle (Huisamen et al. 1994). EDL and SOL muscles were surgically removed from the animals and sutures were attached to each end (tendons) of the muscles. EDL and SOL muscles were mounted vertically on a Radnoti (Monrovia, CA, USA) glass stimulating apparatus with platinum electrodes and were immersed in a 20-ml bathing chamber containing the incubation medium. The muscle sutures were attached to a movable isometric force transducer and to a stationary anchor, which allowed muscles to be stretched until both maximal forces for a given frequency and the frequency producing maximal isometric tetanic force (Tmax) were obtained. It is fundamental that muscles are allowed to equilibrate in the new bathing environment (equilibration period) after dissection, and mounting and stretching procedures. It is only after this initial equilibration period that muscles were fatigued and then they are allowed to recover from fatigue. Ten muscles from five mice from each experimental group were utilized for obtaining the averaged data shown in Figs 1 and 2. The resting tension and the stimulatory voltage (provided by a Grass digital stimulator) were adjusted to produce Tmax. The stimulation pattern for these experiments was completely automated after the muscles were mounted. A Powerlab/400 E series control system (ADInstruments, Mountain View, CA, USA) was used to drive a digital Grass stimulator. Chart for Windows v4.0.1 (ADInstruments) was used to collect, digitize, analyse and store the data to a PC.
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We have previously demonstrated (Brotto et al. 2001, 2002) that fatiguing muscles with a frequency that produces Tmax maximizes the detection of effects associated with the contractile machinery and not the excitation–contraction coupling (ECC) process. Therefore, after Tmax was determined, the intact muscles were allowed to equilibrate for 20 min in the modified Ringer solution. During equilibration, muscle strips were stimulated with 100-Hz (EDL) or 70-Hz (SOL), 330-mA, 500-ms electrical pulse trains administered with a periodicity of 1 min to generate Tmax. Following equilibration, the muscles from the fatigue group were subjected to a 5-min fatiguing protocol consisting of the same stimulatory pattern administered at a 1-s periodicity (i.e. 50% duty cycle). Thereafter, the periodicity of the stimulus train was returned to 1 min intervals and the muscles were allowed to recover for 30 min in the absence of caffeine and for 30 min in the presence of 20 mM caffeine. Caffeine was mixed in a small volume of the modified Ringer solution and added to the chambers to produce a final concentration of 20 mM in the bathing chamber. All force data were normalized to the last tetanic contraction at the end of the equilibration period and just prior to the start of the fatiguing protocol (i.e., Tmax= 100%). Absolute force, normalized per cross-sectional area (in kg cm–2) was determined at the end of the equilibration period by the following relationship:
Force = (g force) x (muscle length) x 1.06/muscle weight where 1.06 represents the density of the muscle strips.
Triton-skinned muscle fibres
Muscle dissection. All experiments followed the protocols as described in Brotto & Nosek (Brotto & Nosek, 1996; Brotto et al. 2001). The composition of all solutions was calculated by using a computer program (Borland International, Scotts Valley, CA, USA) employing the stability constants that are commonly used in our laboratory (Godt & Lindley, 1982). Intact muscles used for the fatigue studies were dissected in a solution containing (mM): Mg2+ 1, Mg ATP 1, phosphocreatine 15, potassium methanesulphonate (KMS) 140, imidazole 50 and EGTA 20; ionic strength, 170, pCa < 8.5, pH 7.0 at 4°C. This solution also contained a cocktail of protease inhibitors to protect the fibres from the damaging effects of proteolysis (0.1 mM phenylmethylsulphonyl fluoride, 0.1 mM leupeptin, 1.0 mM benzamidine, 10 µM aprotinin).
Triton permeabilization. After single muscle fibres were dissected as described above, they were exposed for 30 min to the same dissecting solution described above, except that this solution also contained 0.5% w/w Triton X-100 (a non-ionic detergent that permeabilizes the sarcolemmal membrane and all subcellular organelles). This is a fundamental step when attempting to accurately control Ca2+ and other ion concentrations near the contractile proteins (Brotto et al. 1995; Brotto & Nosek, 1996).
Set up of mechanical recordings. Triton-skinned muscle fibres were carefully washed for 60 min to remove any residual Triton X-100. They were then mounted in between an optoelectric force transducer (Scientific Instruments GMBH, Heidelberg, Germany) and a movable arm by wrapping the fibres three times around small stainless steel wires. Others and we (Maughan et al. 1995; Brotto & Nosek, 1996) have demonstrated that the central part of muscle fibres mounted this way is undamaged. Muscle fibres were bathed in a solution containing (mm): Mg2+ 1.0, Mg ATP 5.0, phosphocreatine 15, KMS 100.0, imidazole 20.0 and EGTA 5.0; ionic strength 200, pCa 8.5–4.0, pH 7.0 at 25 ± 1°C, in 2.5-ml troughs milled in a spring-loaded Plexiglas plate.
Maximum Ca2+-activated force and force–pCa relationships.
After mounting, only a small part (300 µm) of the single fibre remains free in between the mounting wires. Triton-skinned muscle fibres were stretched by 30% above slack length and sarcomere length was adjusted to 2.6 ± 0.1 µm by using its laser diffraction pattern (Brotto & Nosek, 1996). Triton-skinned muscle fibres were briefly exposed to pCa 6.0 to secure them to the wires; they were subsequently relaxed in pCa 8.5 and then exposed to solutions of varying Ca2+ concentrations (pCa 8.5–4.0) in order to determine the force–pCa relationship. Each force–pCa relationship was analysed as previously described (Brotto et al. 1995, 2001; Brotto & Nosek, 1996). Maximum Ca2+-activated force (Fmax) was recorded and normalized to the cross-sectional area of each fibre and to the maximal force produced by each fibre (100%, Fmax). Computer programs (Sigma Plot 5.0 and Origin 6.0, Jandel Scientific) were used to fit the force–Ca curve for each fibre to the Hill equation:
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Silver-enhanced SDS-PAGE analysis of single Triton-skinned muscle fibres
These experiments followed previously established protocols (Brotto et al. 2000, 2001), as modified by Jin et al. (2003). In brief, total protein extract of each Triton-skinned EDL and SOL muscle fibre used for the force–pCa experiments was resolved by SDS-PAGE on 14% Laemmli gels with an acrylamide/bisacrylamide ratio of 180: 1 and visualized by silver stain. Samples were equally loaded by calculating the volume of each fibre. Only Triton-skinned muscle fibres for which a complete set of data was obtained were utilized in this report (i.e. force–pCa relationships and SDS-PAGE were performed on the same fibre). In addition, as previously reported (Brotto et al. 2000, 2001), actin could be used as an internal control for even loading, because its densitometric signal was never affected under any experimental condition. Densitometric analysis of the SDS-PAGE was performed using the National Institutes orf Health Image program, version 1.61, on images scanned at 600 dpi of all malarial and control Triton-skinned muscle fibres used for the force–pCa experiments. Density levels for control bands were normalized to 100% and compared to the density of malarial fibres.
Statistics
SigmaStat 3.0 software (SPSS, Chicago, IL, USA) was used for all statistical analyses. The criterion for statistical significance was a P
0.05. For statistical analysis of parametric sets of data, one-way analysis of variance (ANOVA, SigmaStat) followed by Tukey's post hoc test was used. For non-parametric sets of data, Kruskal–Wallis one-way analysis of variance on ranks was used. Sets of data comprising the force–pCa relationships and gel densitometry were tested with Kruskal–Wallis one-way analysis of variance on ranks followed by Dunn's method for multiple comparisons.
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Results |
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In this study, mice with parasitaemia of 35% (ranging from 31 to 39%) were selected because they displayed symptoms that are comparable with those reported in humans. Under our experimental conditions, the level of 20% parasitaemia was the lower threshold for a muscle-related phenotype, while animals with more than 42% began to manifest brain dysfunction symptoms (e.g. head deviation and coma), although it is known whether neurological signs can develop at lower levels of parasitaemia (Bagot et al. 2004). No animals with neurological-related symptoms were employed in our study. After the initial bolus injection with infected blood, mice blood smears were checked daily for the identification of the targeted level of parasitaemia, which was achieved within 3–6 days after the initial injection.
Intact muscles
Figure 1A and B summarizes the Tmax data obtained in intact SOL muscles before, during and after fatiguing stimulation. In Fig. 1A, Tmax was averaged and normalized to the amount of absolute force produced per cross-sectional area (Tmax-CSA). As seen, SOL muscles from malarial mice produced significantly less force throughout the protocol. In Fig. 1B, the same data were normalized as a percentage of Tmax. Control SOL muscles typically fatigue to 50% of the initial equilibration pre-fatigue Tmax at the end of an intermittent fatiguing protocol (Brotto et al. 2002). This typical response of soleus muscles is also observed here in control muscles (see Fig. 1B). In contrast, SOL muscles from malarial mice fatigued to approximately 20% of pre-fatigue Tmax levels. After a 45-min recovery period, when control muscles had returned to essentially their pre-fatigue Tmax levels, malarial SOL muscles recovered to a significantly lesser extent. To test whether or not any damage was caused to the contractile proteins during fatiguing stimulation, both control and malerial SOL muscles were exposed to a high concentration of caffeine to enhance calcium release from the SR and overcome any decrement in the ECC process known to occur with fatiguing stimulations. Exposure to caffeine had no significant effect on control muscles (suggesting that no damage to either the ECC process or the contractile proteins occurred with fatiguing stimulation) but did return the Tmax of malarial muscles to their pre-fatigue levels (suggesting no damage to the contractile proteins with fatiguing stimulation but significant decrement in the ECC process).
Figure 2A and B summarizes the same type of experiments as shown in Fig. 1A and B, but for intact EDL muscles. The Tmax-CSA is significantly greater in EDL than SOL muscle. Control EDL muscles respond to fatiguing stimulation with a greater decrease in Tmax than SOL muscles. Unlike SOL muscles, they do not return to control levels after 30 min of recovery; caffeine is required for complete recovery, suggesting impairment of the ECC process in control EDL muscles. The enhanced inhibitory response to fatiguing stimulation observed in SOL muscles from malarial mice is also observed in EDL muscles from the same mice. Caffeine was able to fully restore Tmax in EDL muscles from malarial mice suggesting that there was no damage done by the fatiguing stimulation to the contractile proteins.
Single Triton-skinned muscle fibres
In order to specifically test whether or not the contractile proteins of muscles from malarial mice are modified, force–pCa relationships were determined in SOL (Fig. 3A; control, n= 20; malarial, n= 18) and EDL (Fig. 3B; control, n= 20; malarial, n= 18) muscle fibres (see also Table 1). In both muscle types, the force–pCa curves were significantly shifted to the right (Ca2+ sensitivity was decreased) in muscle fibres from malarial animals. Furthermore, the cooperativity index (i.e. Hill coefficient; related to the steepness of the force–pCa relationship and an index of the cooperativity of the contractile proteins) was significantly decreased in both muscle types from malarial mice. In addition, Fmax normalized to the cross-sectional area (Fmax-CSA) was significantly decreased in single Triton-skinned muscle fibres of EDL and SOL muscles of malarial mice. These results are consistent with our findings in intact muscles. Because in Triton-skinned muscle fibres the ECC system is destroyed by the permeabilization process and only contractile-related proteins are present in these preparations, they faithfully express events associated with the contractile apparatus. Therefore, it is possible to infer from these experiments that malaria infection directly affected the force generation capacity by modifying the contractile proteins (see Tables 1 and 2). In addition, when we tested Triton-skinned muscle fibres dissected from fresh muscles obtained from two control and two malarial mice not previously exposed to any experimental intervention; we found essentially identical results, indicating that functional and biochemical modifications are not caused by the fatiguing protocols (data not shown).
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We analysed the protein content of the skinned fibres used for the force–pCa studies. Densitometry analyses were performed on all bands with the density of the protein bands from the control muscle normalized to 100%. We found a significant decrease (from between 15 and 45%) in protein content for six specific proteins in SOL and EDL fibres from malarial mice: myosin heavy chain (MHC), troponin T (TnT), tropomyosin, troponin C (TnC), myosin light chain type II (MLC2) and myosin light chain type III (MLC3) (see details in Table 2). Representative SDS-PAGE analysis is shown in Fig. 4A (SOL) and Fig. 4B (EDL). Both SDS-PAGE and force–pCa data were obtained from the same fibres. These data strongly suggest that malarial muscles are weaker and more fatigable because of a loss of essential contractile proteins. In addition, comparative analysis of muscle fibres from the four control and malarial muscles not exposed to any experimental intervention (data not shown) also exhibited the same pattern of protein loss, suggesting that such loss was not induced or aggravated by the fatiguing protocols or the generation of the force–pCa relationships, where exposure to high calcium could induce damage.
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Discussion |
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In intact muscles, tetanic force can be influenced by both the force-generating capabilities of the contractile proteins and by the level of calcium which reaches these proteins, controlled by the ECC process. However, individual skinned muscle fibres, in which the sarcolemma has been chemically removed, generate force that is only controlled by the calcium level of the bathing medium. Our studies demonstrate that Fmax and Ca2+ sensitivity of the contractile proteins are reduced in both EDL and SOL malarial muscles. These experiments suggest that there is direct damage caused by malarial infection to the contractile proteins. This was confirmed in our biochemical studies. It was shown in the present study that Triton-skinned muscle fibres from malarial mice display a significant decrease in the density of MHC, TnT, tropomyosin, TnC, MLC2 and MLC3. Unquestionably, even a partial loss of the aforementioned proteins will cause a decrease of force produced per cross-bridge unit. Thus, the loss or decreased content of such proteins will certainly be translated into functional modifications. It is important to note that additional analysis of muscle fibres from malarial muscles not exposed to any experimental intervention also revealed the same pattern of protein loss, suggesting that such loss was not induced or aggravated by the skinned fibre experiments, where exposure to high Ca2+ could have potentially induced damage. Thus, the loss of protein content seems rather to be the intrinsic result of malarial infection itself.
In our intact muscle experiments, in which force production is controlled both by the ECC process and the force-generating capabilities of the contractile proteins, we used stimulating protocols that maximize and optimize the detection of changes within the contractile machinery, because when muscles are stimulated with a frequency that produces Tmax, they are necessarily working at the plateau of the force–frequency relationship for the intact muscle and the plateau of the force–Ca2+ relationship of the contractile proteins. At this plateau level, Tmax can be achieved at a wide range of intracellular Ca2+ (e.g., from 5 µM to 100 µM), thus, even large decreases in Ca2+ due to inhibition of the ECC process may not be translated into decreases in force. Under non-fatigue conditions, normalized Tmax values for both intact control EDL and SOL muscles were equal to corresponding Fmax values for skinned fibres confirming that the intact muscles under these conditions were producing maximal force and that the ECC process was not limiting. In fact, the remarkable agreement between the cross-sectional levels of force obtained in both intact muscles and in Triton-skinned muscle fibres reported here, strongly suggests that our experimental protocols are optimized for the detection of modifications occurring on the contractile proteins. The same was true for malarial EDL and SOL muscles under non-fatigue conditions.
Both intact control EDL and SOL muscles responded typically to fatiguing stimulation. The loss of force during fatiguing stimulation is complicated, being in part due to changes in the intracellular milieu and to potential changes in the ECC process and in the force-generating capabilities of the contractile proteins. In control EDL muscles, complete recovery to pre-fatigue Tmax levels was only achieved after treatment with caffeine, a stimulant of the ECC process (specifically Ca2+ release from the SR). This suggests that fatiguing stimulation has no permanent effect on the contractile proteins but does inhibit the ECC process. EDL muscles from malarial mice fatigued to a greater extent than control EDL muscles but, nevertheless, returned to pre-fatigue Tmax levels after the application of caffeine. These results suggest that fatiguing stimulation has no permanent effect on the contractile proteins of malarial EDL muscles but has a greater inhibitory effect on the ECC process than in control EDL muscles. Intact control SOL muscles responded differently to fatiguing stimulation than intact EDL muscles; they fatigued less and did not require caffeine to return Tmax to pre-fatiguing levels. Thus, fatiguing stimulation does not appear to significantly inhibit either the ECC process or have long-term effects on the contractile proteins in control SOL muscles. However, SOL muscles from malarial mice fatigued to a greater extent and did require caffeine for the return of Tmax to pre-fatigue levels. These results suggest that the ECC process is disrupted by fatiguing stimulation in SOL muscles infected with malaria.
Our findings, as revealed by SDS-PAGE analysis of Triton-skinned muscle fibres, demonstrate that malaria triggers a significant loss of the contractile machinery proteins MHC, TnT, tropomyosin, TnC, MLC2 and MLC3. The decrease in their net content could account for the effects on Tmax and Fmax in intact and skinned muscles, as a smaller number of functional cross-bridges would be anticipated by the loss of these proteins, which would cause a net decrease in the amount of force produced by the muscle fibres.
In agreement, muscle fibre alterations, including disorganization of the contractile machinery, have been reported by Carmona et al. (1996) in skeletal muscles infected with malaria. Furthermore, significant changes in serum levels of creatine kinase and myoglobin have been reported in humans infected with falciparum malaria (Miller et al. 1989b; Davis et al. 1999, 2000). Such elevation in serum levels of creatine kinase and myoglobin is normally caused by processes that can be divided into genetic, ischaemic, metabolic, inflammatory and traumatic disorders of muscle.
It is important to note that here we described the effects at steady-state levels (i.e. force levels at the end of the equilibration period, at the end of fatigue and at the end of recovery, and in Triton-skinned muscle fibres the peak steady-state force produced at each Ca2+ concentration). Therefore, our studies do not reveal information regarding kinetic parameters (e.g. rates of force development and rates of fatigue/recovery). In addition, our studies were designed to maximize the detection of functional and biochemical modifications occurring on the contractile proteins and not on the ECC system. Although additional analyses of our data (i.e. by comparing the relative decrease in Tmax between control and malarial muscles with the relative Fmax of the skinned muscle fibres; data not shown) revealed that the ECC process was not the main site of the effects of malaria, this observation may have been caused by the protocols chosen here and not necessarily because of a lack of an effect of malaria infection on the ECC process. It is possible that if muscles were fatigued with low frequencies of stimulation that significant effects at the ECC level could also be observed, but this was beyond the scope of our study.
Our studies do not provide information on the modification pathways involved with the protein loss observed in single muscle fibres from malarial mice. However, malaria is known to trigger inflammatory (Clark & Cowden, 2003) and oxidative stress (Pabon et al. 2003) responses. Such changes in intracellular milieu will unquestionably produce muscle cell damage (Clark & Cowden, 2003) and may be responsible for the damage we report here because strong and highly reactive free radicals are generated under these conditions (Closa & Folch-Puy, 2004). For example, hydroxyl radicals are generated in tissues where neutrophil infiltration occurs (Closa & Folch-Puy, 2004). Such free radicals can directly attack proteins, causing direct damage to the contractile machinery (Kaneko et al. 1993; Callahan et al. 2001). We have recently reported (Brotto et al. 2000, 2001) that diaphragm muscles fatigued under hypoxic fatigue display functional and biochemical modifications similar to those reported here for the malarial muscles, characterized by a reduced calcium sensitivity, decreased force output and partial degradation of troponins C and I. We also determined that functional and biochemical modifications observed under hypoxic fatigue were mediated by free radicals.
It is plausible to speculate that the combination of inflammatory and oxidative stresses can significantly alter the intracellular milieu of malarial muscle cells leading to muscle damage (Brotto et al. 2000). This may well explain muscle-related symptoms referred by patients with malaria and it may warrant additional studies to further explore the involvement of free radicals and the possibility of prevention/amelioration of malaria symptoms by the use of anti-oxidants. In support of our hypothesis, Yeudall et al. (2002) have recently reported that improvements in the micronutrient adequacy of diets in rural Malawian children were associated with a favourable increase in indices of lean body mass and reductions in the incidence of anaemia and common infections such as malaria.
We believe that our novel findings of contractile damage confirmed at the biochemical and functional levels may provide new insights about the multitude of muscle-related symptoms associated with malaria.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Booth FW & Vyas DR (2001). Genes, environment, and exercise. Adv Exp Med Biol 502, 13–20.[Medline]
Brotto MA, Andreatta-Van Leyen S, Nosek CM, Brotto LS & Nosek TM (2000). Hypoxia and fatigue-induced modification of function and proteins in intact and skinned murine diaphragm muscle. Pflugers Arch 440, 727–734. 10.1007/s004240000327[CrossRef][Medline]
Brotto MAP, Fogaca RTH, Creazzo TL, Godt RE & Nosek TM (1995). The effect of 2,3-Butanedione 2-monoxime (BDM) on ventricular trabeculae from the avian heart. J Muscle Res Cell Motil 16, 1–10.[CrossRef][Medline]
Brotto
MA
&
Nosek
TM (1996). Hydrogen peroxide disrupts Ca2+ release from the sarcoplasmic reticulum of rat skeletal muscle fibers. J Appl Physiol
81, 731–737.
Brotto MA, Nosek TM & Kolbeck RC (2002). Influence of ageing on the fatigability of isolated mouse skeletal muscles from mature and aged mice. Exp Physiol 87, 77–82.[Abstract]
Brotto MAP, Van Leyen SA, Brotto LS, Jin JP, Nosek CM & Nosek TM (2001). Hypoxia/fatigue-induced degradation of troponin I and troponin C: new insights into physiologic muscle fatigue. Pflugers Arch 442, 738–744. 10.1007/s004240100587[CrossRef][Medline]
Callahan
LA, Nethery
D, Stofan
D, Dimarco
A
&
Supinski
G (2001). Free radical-induced contractile protein dysfunction in endotoxin-induced sepsis. Am J Respir Cell Mol Biol
24, 210–217.
Carmona M, Finol HJ, Marquez A & Noya O (1996). Skeletal muscle ultrastructural pathology in Serinus canarius infected with Plasmodium cathemerium. J Submicrosc Cytol Pathol 28, 87–91.[Medline]
Clark IA & Cowden WB (2003). The pathophysiology of falciparum malaria. Pharmacol Ther 99, 221–260.[CrossRef][Medline]
Closa D & Folch-Puy E (2004). Oxygen free radicals and the systemic inflammatory response. IUBMB Life 56, 185–191.[Medline]
Davis TM, Pongponratan E, Supanaranond W, Pukrittayakamee S, Helliwell T, Holloway P & White NJ (1999). Skeletal muscle involvement in falciparum malaria: biochemical and ultrastructural study. Clin Infect Dis 29, 831–835.[Medline]
Davis TM, Supanaranond W, Pukrittayakamee S, Holloway P, Chubb P & White NJ (2000). Progression of skeletal muscle damage during treatment of severe falciparum malaria. Acta Trop 76, 271–276. 10.1016/S0001-706X(00)00111-X[CrossRef][Medline]
De Silva HJ, Goonetilleke AK, Senaratna N, Ramesh N, Jayawickrama US, Jayasinghe KS & Amarasekera LR (1988). Skeletal muscle necrosis in severe falciparum malaria. Br Med J (Clin Res Ed) 296, 1039.
Godt
RE
&
Lindley
BD (1982). Influence of temperature upon contractile activation and isometric force production in mechanically skinned muscle fibers of the frog. J Gen Physiol
80, 279–297. 10.1085/jgp.80.2.279
Hoffmann
EJ, Weidanz
WP
&
Long
CA (1984). Susceptibility of CXB recombinant inbred mice to murine plasmodia. Infect Immun
43, 981–985.
Huisamen B, Mouton R, Opie LH & Lochner A (1994). Demonstration of a specific [3H]INS (1,4,5) P3 binding site in rat heart sarcoplasmic reticulum. J Mol Cell Cardiol 26, 341–349. 10.1006/jmcc.1994.1043[CrossRef][Medline]
Jin
JP, Brotto
MA, Hossain
MM, Huang
QQ, Brotto
LS, Nosek
TM, Morton
DH
&
Crawford
TO (2003). Truncation by glu180 nonsense mutation results in complete loss of slow skeletal muscle troponin T in a lethal nemaline myopathy. J Biol Chem
278, 26159–26165. 10.1074/jbc.M303469200
Kaneko M, Masuda H, Suzuki H, Matsumoto Y, Kobayashi A & Yamazaki N (1993). Modification of contractile proteins by oxygen free radicals in rat heart. Mol Cell Biochem 125, 163–169. 10.1007/BF00936445[CrossRef][Medline]
Knochel
JP
&
Moore
GE (1993). Rhabdomyolysis in Malaria. N Engl J Med
329, 1206–1207. 10.1056/NEJM199310143291618
Maughan
DW, Molloy
JE, Brotto
MA
&
Godt
RE (1995). Approximating the isometric force-calcium relation of intact frog muscle using skinned fibers. Biophys J
69, 1484–1490.
Meier S, Krause M, Luthy R, Baumann PC & Markwalder K (1995). [Intensive care aspects in severe tropical malaria: clinical aspects, therapy and prognostic factors]. Schweiz Med Wochenschr 125, 1033–1040.[Medline]
Miller
KL, Silverman
PH, Kullgren
B
&
Mahlmann
LJ (1989a). Tumor necrosis factor alpha and the anemia associated with murine malaria. Infect Immun
57, 1542–1546.
Miller KD, White NJ, Lott JA, Roberts JM & Greenwood BM (1989b). Biochemical evidence of muscle injury in African children with severe malaria. J Infect Dis 159, 139–142.[Medline]
Pabon A, Carmona J, Burgos LC & Blair S (2003). Oxidative stress in patients with non-complicated malaria. Clin Biochem 36, 71–78. 10.1016/S0009-9120(02)00423-X[CrossRef][Medline]
Taylor WR & Prosser DI (1992). Acute renal failure, acute rhabdomyolysis and falciparum malaria. Trans R Soc Trop Med Hyg 86, 361. 10.1016/0035-9203(92)90218-2[CrossRef][Medline]
Yeudall F, Gibson RS, Kayira C & Umar E (2002). Efficacy of a multi-micronutrient dietary intervention based on haemoglobin, hair zinc concentrations, and selected functional outcomes in rural Malawian children. Eur J Clin Nutr 56, 1176–1185. 10.1038/sj.ejcn.1601469[CrossRef][Medline]
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