title: Role of caspase-3 cleaved IP3 R1 on Ca(2+) homeostasis and developmental competence of mouse oocytes and eggs.
abstract: Apoptosis in most cell types is accompanied by altered Ca(2+) homeostasis. During apoptosis, caspase-3 mediated cleavage of the type 1 inositol 1,4,5-trisphosphate receptor (IP3 R1) generates a 95-kDa C-terminal fragment (C-IP3 R1), which represents the channel domain of the receptor. Aged mouse eggs display abnormal Ca(2+) homeostasis and express C-IP3 R1, although whether or not C-IP3 R1 expression contributes to Ca(2+) misregulation or a decrease in developmental competency is unknown. We sought to answer these questions by injecting in mouse oocytes and eggs cRNAs encoding C-IP3 R1. We found that: (1) expression of C-IP3 R1 in eggs lowered the Ca(2+) content of the endoplasmic reticulum (ER), although, as C-IP3 R1 is quickly degraded at this stage, its expression did not impair pre-implantation embryo development; (2) expression of C-IP3 R1 in eggs enhanced fragmentation associated with aging; (3) endogenous IP3 R1 is required for aging associated apoptosis, as its down-regulation prevented fragmentation, and expression of C-IP3 R1 in eggs with downregulated IP3 R1 partly restored fragmentation; (4) C-IP3 R1 expression in GV oocytes resulted in persistent levels of protein, which abolished the increase in the ER releasable Ca(2+) pool that occurs during maturation, undermined the Ca(2+) oscillatory ability of matured eggs and their activation potential. Collectively, this study supports a role for IP3 R1 and C-IP3 R1 in regulating Ca(2+) homeostasis and the ER Ca(2+) content during oocyte maturation. Nevertheless, the role of C-IP3 R1 on Ca(2+) homeostasis in aged eggs seems minor, as in MII eggs the majority of endogenous IP3 R1 remains intact and C-IP3 R1 undergoes rapid turnover.
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Fissore
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D047108:Embryonic Development; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006706:Homeostasis; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D059748:Proteolysis; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D019284:Thapsigargin; D053148:Caspase 3; D002118:Calcium