Yadav, VK and Lakshmi, G and Medhamurthy, R (2004) Prostaglandin $F_2_a$-mediated activation of apoptotic signaling cascades in the corpus luteum during apoptosis: Involvement of caspase activated DNase. [Preprint]
Prostaglandin (PG) F2a acting via a G proteincoupled receptor has been shown to induce apoptosis in the corpus luteum of many species. Studies were carried out to characterize changes in the apoptotic signaling cascade/s culminating in luteal tissue apoptosis during PGF2a-induced luteolysis in the bovine species, in which initiation of apoptosis was demonstrable at 18h after exogenous PGF2a treatment. Analysis of intrinsic arm of apoptotic signaling cascade elements revealed that PGF2a injection triggered increased ratio of Bax to Bcl-2 in the luteal tissue as early as 4h post treatment that remained elevated till 18h. This increase was associated with the elevation in the active caspase-9 and 3 protein levels and activity (p < 0.05) at 4-12h, but a spurt in the activity was seen only at 18h post treatment that could not be accounted for by the changes in the Bax/Bcl-2 ratio or changes in translocation of Bax to mitochondria. Examination of luteal tissue for FasL/Fas death receptor cascade revealed increased expression of FasL and Fas at 18h accompanied by a significant (p < 0.05) induction in the caspase-8 activity and tBid levels. Further, intrabursal administration of specific caspase inhibitors, downstream to the extrinsic and intrinsic apoptotic signaling cascades, in a pseudopregnant rat model revealed a greater importance of extrinsic apoptotic signaling cascade in mediating luteal tissue apoptosis during PGF2a treatment. The Dnase responsible for PGF2a-induced apoptotic DNA fragmentation was found to be a Ca++/Mg++ dependent, temperature sensitive DNase, optimally active at neutral pH conditions. This putative DNase was inhibited by the recombinant inhibitor of caspase activated DNase (CAD), and immunodepletion of CAD from luteal lysates abolished the observed DNA fragmentation activity. Together, these data demonstrate for the first time temporal and spatial changes in the apoptotic signaling cascades during PGF2a-induced apoptosis in the corpus luteum.
|Keywords:||corpus luteum;Apoptosis;physiology;signaling cascades;FasL;Bax|
|Department/Centre:||Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)|
|Date Deposited:||16 Feb 2005|
|Last Modified:||16 Jan 2013 11:37|
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