Proteome analysis of testis from infertile protein C inhibitor-deficient mice reveals novel changes in serpin processing and prostaglandin metabolism.
Serine protease inhibitors (serpin) have therapeutic potential in a variety of pathogenic processes, ranging from thrombosis and altered immune response to liver cirrhosis. To investigate the physiological effects of protein C inhibitor (PCI, serpinA5), its gene was inactivated in a mouse model, resulting in male infertility. In the present report, 2D differential gel electrophoresis was utilized to investigate the molecular mechanisms for PCI involvement in male reproduction. Comparing the testes proteomes of three PCI-knockout mice with three wild types demonstrated similar patterns with the exception of a massive upregulation of prostaglandin reductase 1 (tenfold; p < 0.002) and the complete shifts in the molecular weights of serpinA1C and serpinA3K. All these PCI-dependent proteome changes were immunologically verified. Unbiased proteome analysis indicated that inactivation of serpinA5 strongly influenced both the protein species pattern of other A-clade serpins as well as prostaglandin metabolism in the testes.
Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Hanjiang
H
Yang
Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Felix Christof
FC
Wahlmüller
Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Pavel
P
Uhrin
Center for Physiology and Pharmacology, Institute of Physiology, Medical University of Vienna, Vienna, Austria.
Roland
R
Baumgartner
Clinical Department of Laboratory Medicine, Proteomics Core Facility, Medical University of Vienna, Vienna, Austria.
Goran
G
Mitulovic
Division of Clinical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
Bettina
B
Sarg
Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Margarethe
M
Geiger
Center for Physiology and Pharmacology, Institute of Physiology, Medical University of Vienna, Vienna, Austria.
Maria
M
Zellner
2D differential gel electrophoresis; Drug-target validation; Infertility; Prostag-landin reductase 1; Serpin