The ASK1-Signalosome regulates p38 MAPK activity in response to levels of endogenous oxidative stress in the <i>Klotho</i> mouse models of aging

C-C Hsieh; Makoto Kuro-o; Kevin P. Rosenblatt; Reynolds Brobey; John Papaconstantinou

doi:doi:10.18632/aging.100194

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Research Paper Volume 2, Issue 9 pp 597—611

The ASK1-Signalosome regulates p38 MAPK activity in response to levels of endogenous oxidative stress in the Klotho mouse models of aging

Figure 1. Klotho ablation activates the ASK1-signalosome - p38 MAPK pathway. (A) Klotho^(-/-) exhibits low levels of the inhibitory (SH)₂Trx-ASK1 complex. Western blot analysis of levels of Trx co-immunoprecipitated with ASK1 (IP: ASK1) in liver extracts of Klotho^(-/-) (129) and WT (129) mice. (B) MKK3/MKK6 activity is elevated in Klotho^(-/-). Western blot analysis of levels of MKK3/6 catalytic site amino acids, P-Ser189/207 in livers of Klotho-/- and WT 129 mice. (C) p38 activity is elevated in Klotho^(-/-). Western blot analyses of levels of the p38 MAPK catalytic site amino acids, P-Thr180/Tyr182, in livers of Klotho (-/-) (129) and WT (129) mice. The bar graphs depict the mean +/- SE of samples from Klotho^(-/-) (129; #20, 21, 22) and from WT (129; #23, 24, 25).