title: Load-induced focal adhesion mechanotransduction is altered with aging in the Fischer 344/NNiaHSd x Brown Norway/BiNia rat aorta.
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.
authors.affiliation: Department of Pharmacology, Physiology, and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755-1090, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Rice
authors.forename: D H
authors.initials: DH
authors.lastname: Desai
authors.forename: R S
authors.initials: RS
authors.lastname: Kinnard
authors.forename: R
authors.initials: R
authors.lastname: Harris
authors.forename: G L
authors.initials: GL
authors.lastname: Wright
authors.forename: E R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D051419:Paxillin / Q000235:genetics / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051419:Paxillin; C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D020742:rhoA GTP-Binding Protein