RESUMO
The serpin alpha2-antiplasmin (alpha2-AP) is the major circulating inhibitor of plasmin; it plays a determining role in the regulation of intravascular fibrinolysis, In addition to blood plasma, plasmin formation occurs in various organs where it is thought to fulfill a spectrum of functions not restricted to clot lysis. Alpha2-AP is synthesized by hepatocytes, but other possible sites of production have not been investigated. To explore the potential extravascular contribution of alpha2-AP in the regulation of proteolysis, we have isolated the murine alpha2-AP cDNA and determined its mRNA distribution in adult tissues. In addition to liver, kidneys are major sites of alpha2-AP mRNA accumulation in the mouse. The transcript is present in epithelial cells lining the convoluted portion of proximal tubules, and its accumulation is under androgen control. Human kidneys also contain high levels of alpha2-AP mRNA. Moderate amounts Of alpha2-AP mRNA are detected in other murine tissues such as muscle, intestine, central nervous system, and placenta. Our observations indicate that alpha2-AP can be synthesized in a number of tissues, where it could function as a distal regulator of plasmin-mediated extracellular proteolysis.
Assuntos
Rim/metabolismo , Fígado/metabolismo , Transcrição Gênica , alfa 2-Antiplasmina/biossíntese , Sequência de Aminoácidos , Animais , Bovinos , Clonagem Molecular , Feminino , Humanos , Rim/citologia , Fígado/citologia , Masculino , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Orquiectomia , Especificidade de Órgãos , Gravidez , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Homologia de Sequência de Aminoácidos , Ativador de Plasminogênio Tecidual/biossíntese , Ativador de Plasminogênio Tipo Uroquinase/biossíntese , alfa 2-Antiplasmina/químicaRESUMO
A search for inhibitors of urokinase-type plasminogen activator (uPA) in the male and female murine genital tracts revealed high levels of a uPA ligand in the seminal vesicle. This ligand is functionally, biochemically and immunologically indistinguishable from protease-nexin I (PN-I), a serpin ligand of thrombin and uPA previously detected only in mesenchymal cells and astrocytes. A survey of murine tissues indicates that PN-I mRNA is most abundant in seminal vesicles, where it represents 0.2-0.4% of the mRNAs. PN-I is synthesized in the epithelium of the seminal vesicle, as determined by in situ hybridization, and is secreted in the lumen of the gland. PN-I levels are much lower in immature animals, and strongly decreased upon castration. Testosterone treatment of castrated males rapidly restores PN-I mRNA levels, indicating that PN-I gene expression is under androgen control.
