Sex differences in the response to oxidative and proteolytic stress.

ABSTRACT

Sex differences in diseases involving oxidative and proteolytic stress are common, including greater ischemic heart disease, Parkinson disease and stroke in men, and greater Alzheimer disease in women. Sex differences are also observed in stress response of cells and tissues, where female cells are generally more resistant to heat and oxidative stress-induced cell death. Studies implicate beneficial effects of estrogen, as well as cell-autonomous effects including superior mitochondrial function and increased expression of stress response genes in female cells relative to male cells. The p53 and forkhead box (FOX)-family genes, heat shock proteins (HSPs), and the apoptosis and autophagy pathways appear particularly important in mediating sex differences in stress response.