Received February 9, 2007
Revised March 15, 2007
Accepted after revision May 24, 2007
Uniaxial Stretch-Induced Regulation of MAP Kinase, Akt and p70 S6 Kinase in the Aging Fischer 344 X Brown Norway Rat Aorta
Kevin M Rice 1,
Devashish H Desai 1,
Deborah L Preston 1,
Paulette S Wehner 1,
Eric R Blough 1*
1 Marshall University
* To whom correspondence should be addressed. E-mail: blough{at}marshall.edu.
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Abstract |
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The effects of aging on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signaling molecules, which may be of particular importance in mediating numerous cellular responses including control of cell growth, differentiation and adaptation are the proteins associated with the mitogen activated protein kinase (MAPK) signaling systems. MAPKs in conjunction with the p70s6k signaling cascade have emerged as critical components for regulating numerous mechanotrasduction related cellular responses. Here we investigate the ability of a uniaxial stretch to activate the MAPK and p70s6k pathways in adult (6 mo old), aged (30 mo old) and very aged (36 mo old) Fischer 344/NNiaHSd X Brown Norway/BiNia (FBN) rats. Western blotting of the MAPK family proteins extracellular signal-regulated kinase (Erk) 1/2, p38-, and c-Jun NH2 -terminal kinase (JNK)-MAPKs showed differential expression and activation between these proteins with age. An acute 15 min interval of 20% uniaxial stretch using an ex vivo aortic preparation demonstrated similar regulation of Erk1/2, p38-, and JNK MAPK. However, aging altered uniaxial induced p70s6k pathway signaling. These observations confirm previous data demonstrating MAPK proteins are mechanically regulated, and in addition, suggest p70s6k signaling expression and activation are controlled differently with aging. Taken together, these data may help explain in part, the age related changes in vascular morphology, function and response to injury.
Key Words:
Ageing, Aorta, Cell signalling