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Load-induced focal adhesion mechanotransduction is altered with aging in the Fischer 344/NNiaHSd × Brown Norway/BiNia rat aorta

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Abstract

The focal adhesion kinase (FAK) pathway has emerged as a critical component for mediating numerous cellular responses including control of cell growth, differentiation, and adaptation. Here we compared the expression, basal activation, and the ability of increased intraluminal pressure to activate FAK and focal adhesion-associated proteins in the aorta of adult (6 months old) and very aged (36 months old) Fischer 344/NNiaHSd X Brown Norway/BiNia (F344/NXBN) rats. Immunoblot analysis showed increases in the aortic content of FAK (15%), FAK related non-kinase (p41-FRNK) (28%), Src (92%), RhoA (41%), and paxillin (23%) in the very aged aortae. Increased age significantly changed the basal phosphorylation status of FAK and paxillin. Application of aortic intraluminal pressure (200 mm Hg) amplified the phosphorylation of FAK (Tyr 925), Src (Tyr 416), and paxillin (Tyr 188) in adult animals while aortic loading in the very aged animals failed to induce FAK (Tyr 925) phosphorylation. Aging did not alter the load-induced regulation of RhoA; however, FRNK (p41) translocation between cytosolic and membrane compartments was increased. These results confirm previous observations that FAK and focal adhesion-associated proteins are mechanically regulated and expand these studies to suggest that FAK mechanotransduction is altered with aging.

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Acknowledgments

This study was supported by National Institute on Aging Grants AG-20370, AG-027103 to E.B., NIH Grant RR16477 to R.H., and by NSF EPSCOR to Marshall University.

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Authors and Affiliations

  1. Department of Pharmacology, Physiology, and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA

    K. M. Rice, D. H. Desai, G. L. Wright & E. R. Blough

  2. Laboratory of Molecular Physiology, Suite 311, Science Bldg, Department of Biological Sciences, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755-1090, USA

    R. S. Kinnard & E. R. Blough

  3. Department of Biological Sciences, West Virginia State University, Institute, WV, USA

    R. Harris

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  1. K. M. Rice
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  2. D. H. Desai
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  3. R. S. Kinnard
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  4. R. Harris
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  5. G. L. Wright
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  6. E. R. Blough
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Correspondence to E. R. Blough.

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Rice, K.M., Desai, D.H., Kinnard, R.S. et al. Load-induced focal adhesion mechanotransduction is altered with aging in the Fischer 344/NNiaHSd × Brown Norway/BiNia rat aorta. Biogerontology 8, 257–267 (2007). https://doi.org/10.1007/s10522-006-9066-2

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  • DOI: https://doi.org/10.1007/s10522-006-9066-2

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