Heterologous expression of human phosphodiesterase 3A enhances oxidative stress resistance in yeast

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NHLBI	SIG-4

Authors

• DK Rhee
• JC Lim
• SC Hockman
• F Ahmad
• VC Manganiello

Abstract

All organisms have evolved to overcome environmental stress with low metabolic rate and protective antioxidant activity, which is able to slow down ageing or senescence during the life span. cAMP/PKA signaling pathway is directly correlated with the increased resistance to H2O2 and the extension of life span in yeast cells. PDEs control cAMP in regulating the cell cycle and are components of the RAS/cAMP pathway that mediates general stress responses. Here, we used S. cerevisiae as a model system to study human PDE3A-mediated response to exogenous oxidative stress. hPDE3A enhances calcineurin activity and upregulates YAP1-dependent gene expression, which in turn leads to the increased expression of cellular target genes. When the recovery of PDE3A-overexpressing cells against H2O2 were examined by comparing thiol redox state of Tsa1p, the recovery from H2O2 in hPDE3A-overexpressing cells was faster than in mock, by upregulating Gcn2-dependent Srx1, which keeps Tsa1p active by reactivating hyperoxidized Tsa1p.

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