| 19062170 |
Soto P, Smith LC: BH4 peptide derived from Bcl-xL and Bax-inhibitor peptide suppresses apoptotic mitochondrial changes in heat stressed bovine oocytes. Mol Reprod Dev. 2009 Jul;76(7):637-46.
Mitochondria play an important role in the integration and transmission of cell death signals mediated by the Bcl-2 family proteins. Experiments were conducted to determine whether the anti-apoptotic peptides BH4 domain of Bcl-xL (TAT-BH4) and Bax inhibitor peptide (BIP) suppresses heat stress (HS) injury in oocytes by reduction of apoptotic-like events. Cumulus-oocyte complexes (COCs) were matured at 39 degrees C (control) or 41 degrees C (HS) for 21 hr then placed in maturation medium containing 0 or 100 microM BIP in water and 0 or 1 microM TAT-BH4 in dimethyl sulfoxide (DMSO), or a combination of both peptides (BIP + BH4). Peptide effects on embryo development, DNA fragmentation, mitochondrial membrane potential (Delta (Psi) m), and mitochondrial DNA (mtDNA) copy number were measured. All groups were fertilized and cultured in vitro at 39 degrees C for 8 days. Compared to control, HS-treated oocytes induced a decrease in embryo development (P < 0.05), increase in proportion of TUNEL-positive chromatin in oocytes and blastocysts (P < 0.05), and loss of oocyte Delta (Psi) m (P < 0.001). In the presence of BIP or BIP + BH4, development of HS-treated oocytes into blastocysts was increased (P < 0.05). Conversely, COCs matured with TAT-BH4 at 41 degrees C showed reduced embryonic development (P < 0.05). Exposure of HS-treated to each or both peptides resulted in a reduction of TUNEL frequency in oocytes and blastocysts cells derived from these oocytes (P < 0.05). The loss of Delta (Psi) m in HS-treated oocytes was not restored by exposure to BIP + BH4 and there was no effect in mtDNA copy number. In conclusion, the present results show that HS-induced apoptosis in bovine oocytes involves Bax and BH4 domain-dependent pathways. |
1(0,0,0,1) |