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(206) THE PARADOXICAL PROHIBITIN EXPRESSION DURING CERAMIDE-INDUCED APOPTOSIS IN RAT GRANULOSA CELLS. Chowdhury, Indrajit1, 2, Gregory-Bass, Rosalind1, 2, Stiles, Jonathan3, Yao, Xuebiao4, Zeleznik, Anthony5, Thompson, Winston1, 2, 1 Morehouse School of Medicine, Atlanta, Georgia2 Morehouse School of Medicine, Atlanta, Georgia3 Morehouse School of Medicine, Atlanta, Georgia4 Morehouse School of Medicine, Atlanta, Georgia5 University of Pittsburgh, Pittsburgh, Pennsylvania ABSTRACT- Prohibitin is an evolutionary conserved mitochondrial protein that is associated with granulosa cell differentiation, atresia, and luteolysis. Although prohibitin has recently been demonstrated to suppress apoptosis in mammalian cells, its role in granulosa cell death is unknown. In the present study we examined the role of prohibitin in the regulation of apoptosis in rat granulosa cells. Treatment of granulosa cells with a cell-permeable ceramide analog (C8) consistently increased prohibitin content and induced apoptosis in a time and concentration dependent manner. Transfection of granulosa cells with a GFP-prohibitin fusion protein and analysis by fluorescence microscopy, confirmed that prohibitin is predominantly associated with the mitochondria. In response to the apoptotic stimulus, GFP-prohibitin fusion protein appears to translocate from the mitochondria to the cytoplasm and nucleus. Infection of granulosa cells with adenoviral sense prohibitin cDNA resulted in overexpression of prohibitin and markedly attenuated the ability of ceramide to induce apoptosis. These studies indicate that prohibitin mediates apoptosis and is an important factor in ovarian granulosa cell development. KEY WORDS: PROHIBITIN, MITOCHONDRIA, GRANULOSA CELLS, APOPTOSIS |
