Although a cohort of follicles is recruited to develop during the estrous cycle, only a few are selected to ovulate. The remaining members of the cohort undergo atresia. An apoptosis suppressor for granulosa cells in vitro and in vivo, FSH is critical for survival of the growing follicles during development. However, the cellular mechanism by which FSH elicits its antiapoptotic action is still poorly understood.
The inhibitor of apoptosis proteins (IAP; also termed baculovirus inhibitor of apoptosis repeat [BIR]-containing proteins) is a family of intracellular antiapoptotic proteins that were first identified in baculovirus. They are expressed in high abundance in proliferating cells and are suppressed in apoptotic ones. To date, six members have been identified in mammals, including X-linked IAP (XIAP, cIAP-3), human IAP-1 (HIAP-1, cIAP-2), human IAP-2 (HiAP-2, cIAP-1), neuronal apoptosis inhibitor protein (NAIP), survivin, and Livin (termed KIAP in kidney). canadian good neighbor pharmacy
The IAPs are characterized by the presence of a caspase recruitment domain and N-terminal BIR motifs, which are necessary for biological activity. With the exception of NAIP and survivin, the IAPs also contain a C-terminal RING-zinc finger domain believed to be required for protein-protein interactions as well as protein ubiquitination and degradation. Maternal smoking-induced apoptosis of trophoblasts throughout development is associated with decreased XIAP expression. Increased XIAP expression is believed to play a role in the modulation of Fas ligand-induced apoptosis in malignant glioma cells by a proliferation-inducing ligand, a member of the tumor necrosis factor (TNF) family. Studies regarding the mechanisms of action of these antia-poptotic proteins suggested that IAPs modulate the activities of a group of cysteine proteases known as caspases. The XIAP has been shown to be a direct inhibitor of cas-pase-3 and caspase-7, which are involved in the cell surface receptor-dependent cell death pathway, and to suppress the mitochondrial (cytochrome c-mediated) pathway by inhibiting caspase-9 activity. Moreover, mammalian IAPs inhibit caspase-independent apoptosis induced by TNFa in human leukemic cells.