Prostaglandin $F_{2\alpha}-mediated$ Activation of Apoptotic Signaling Cascades in the Corpus Luteum during Apoptosis. Involvement of Caspase Activated DNase

Yadav, Vijay K and Lakshmi, Garimella and Medhamurthy, Rudraiah (2005) Prostaglandin $F_{2\alpha}-mediated$ Activation of Apoptotic Signaling Cascades in the Corpus Luteum during Apoptosis. Involvement of Caspase Activated DNase. In: Journal of Biological Chemistry, 280 (11). pp. 10357-10367.

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Abstract

Prostaglandin $F_2\alpha(PGF_{2\alpha})$ acting via a G protein-coupled 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 $PGF_{2\alpha}-induced$ luteolysis in the bovine species in which initiation of apoptosis was demonstrable at 18 h after exogenous $PGF_{2\alpha}$ treatment. An analysis of intrinsic arm of apoptotic signaling cascade elements revealed that $PGF_{2\alpha}$ injection triggered increased ratio of Bax to Bcl-2 in the luteal tissue as early as 4 hpost treatment that remained elevated until 18 h. This increase was associated with the elevation in the active caspase-9 and -3 protein levels and activity (p < 0.05) at 4-12 h, but a spurt in the activity was seen only at 18 h posttreatment that could not be accounted for by the changes in the Bax/Bcl-2 ratio or changes in translocation of Baxto mitochondria. Examination of luteal tissue for FasL/Fas death receptor cascade revealed increased expression of FasL and Fas at 18 h accompanied by a significant (p < 0.05) induction in the caspase-8 activity and truncated Bid levels. Furthermore, 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 $PGF_{2\alpha}$ treatment. The DNase responsible for $PGF_{2\alpha}$-induced apoptotic DNA fragmentation was found to be $Ca^{2+}/Mg^{2+}$-dependent,temperature-sensitive DNase, and optimally active at neutral pH conditions. This putative DNase was inhibited by the recombinant inhibitor of caspase-activated DNase, and immuno depletion of caspase-activated DNase 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 $PGF_{2\alpha}$-induced apoptosis in the corpus luteum.

Item Type:	Journal Article
Publication:	Journal of Biological Chemistry
Publisher:	American Society for Biochemistry and Molecular Biology Inc.
Additional Information:	Copyright for this article belongs to American Society for Biochemistry and Molecular Biology Inc.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	22 Jan 2007
Last Modified:	16 Jan 2013 11:47
URI:	http://eprints.iisc.ac.in/id/eprint/3319

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