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Pentoxifylline induced signalling events during capacitation of hamster spermatozoa: Significance of protein tyrosine phosphorylation

Seshagiri, PB and Thomas, M and Sreekumar, A and Ray, P and Mariappa, D (2003) Pentoxifylline induced signalling events during capacitation of hamster spermatozoa: Significance of protein tyrosine phosphorylation. In: Cellular And Molecular Biology, 49 (3). pp. 371-380.

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Official URL: http://www.ncbi.nlm.nih.gov/pubmed/12887089

Abstract

To fertilize the oocyte, mammalian spermatozoa must undergo capacitation and acrosome reaction. These events are believed to be associated with various biochemical changes primarily mediated by cAMP, Ca2+ and protein kinases. But the precise signaling mechanisms governing sperm function are not clear. To study this, we used pentoxifylline (PF), a sperm motility stimulant and a cAMP-phosphodiesterase inhibitor, during capacitation and acrosome reaction of hamster spermatozoa. PF induced an early onset of sperin capacitation and its action involved modulation of sperm cell signaling molecules viz., cAMP, [Ca2+](i) and protein kinases. The PF-induced capacitation was associated with an early and increased total protein phosphorylation coupled with changes in the levels of reactive oxygen species. Protein kinase (PK)-A inhibitor (H-89) completely inhibited phosphorylation of a 29 kDa protein while PK-C inhibitor (staurosporine) did not inhibit phosphorylation. Interestingly, PF induced protein tyrosine phosphorylation of a set of proteins (M-r 45-80 K) and a greater proportion of PF-treated spermatozoa exhibited protein tyrosine phosphorylation, compared to untreated controls (82 + 9% vs 34 +/- 10%; p<0.001); tyrosine-phosphorylated proteins were localized specifically to the mid-piece of the sperm. The profile of protein tyrosine phosphorylation was inhibitable by higher concentrations (>0.5 mM) of tyrosine kinase inhibitor, tyrphostin A47. However, at lower (0.1-0.25 mM) concentrations, the compound interestingly induced early sperm capacitation and protein tyrosine phosphorylation, like PF. These results show that protein tyrosine phosphorylation in the mid-piece segment (mitochondrial sheath) appears to be an early and essential event during PF-induced capacitation and a regulated level of tyrosine phosphorylation of sperm proteins is critical for capacitation of hamster spermatozoa.

Item Type: Journal Article
Publication: Cellular And Molecular Biology
Publisher: Cellular And Molecular Biology
Additional Information: Copyright of this article belongs to Cellular And Molecular Biology.
Keywords: spermatozoa (hamster);pentoxifylline;tyrosine phosphorylation;capacitation.
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 24 Nov 2009 10:13
Last Modified: 24 Nov 2009 10:13
URI: http://eprints.iisc.ac.in/id/eprint/17250

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