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 2. Klotho overexpression attenuates the ASK1-signalosome - p38 pathway. (A) Overexpression of Klotho mediates increased levels of the inhibitory (SH)₂Trx-ASK1 complex. Western blot analysis of the levels of Trx co-immunoprecipitated with anti-ASK1 antibody in liver extracts of Klotho overexpressing (EFmKL46) and wild-type (WT Hyb) mice. (B, C) MKK3/MKK6 activity is downregulated in the Klotho overexpressing models. Western blot analysis of levels of the MKK3/6 P-Ser^189/207 in livers of (B) Klotho overexpressing EFmKL46 (#29, 30, 31) and wild-type (WT Hyb; #26, 27, 28) mice and (C) Klotho overexpressing EFmKL48 (#652, 653, 654, 655); and (D) p38 MAPK activity is downregulated by Klotho overexpression. Western blot analysis of levels of p38 MAPK catalytic site amino acids (P-Thr¹⁸⁰/Tyr¹⁸² ) in livers of WT Hyb (#26,27,28) Klotho over-expressing mice (EFmKL46 ; #29,30,31).