Effect of hypoxia on protein tyrosine phosphatase activity and expression of protein tyrosine phosphatases PTP-1B, PTP-SH1 and PTP-SH2 in the cerebral cortex of guinea pig fetus.

The present study tested the hypothesis that the hypoxia in utero results in decreased protein tyrosine phosphatase (PTP) activity in cytosolic and membrane fractions and increased expression of PTPs (PTP-1B, PTP-SH1 and PTP-SH2) in the cytosol and the membrane fraction of the cerebral cortex of guinea pig fetus. In addition, we hypothesize that the increased expression is mediated by nitric oxide (NO). To test this hypothesis, PTP activity in cytosol and cell membrane, and expression in the cytosol and membrane fraction were measured in the cerebral cortex of normoxic, hypoxic and L-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), pretreated hypoxic (L-NAME+Hx) guinea pig fetuses. PTP activity in the cytosolic and membrane fractions was significantly lower in the Hx group as compared to the Nx group. The density of cytosolic PTP-1B, cytosolic PTP-SH1 and PTP-SH2 was increased in the Hx group and this increase was prevented in the L-NAME+Hx group. The data show that pretreatment with L-NAME, an inhibitor of NOS, prevents the hypoxia-induced increased expression of PTP-1B, PTP-SH1 and PTP-SH2 in the membrane and cytosolic fractions of the cerebral cortex of the guinea pig fetus. We conclude that the decrease in PTP activity during hypoxia is not due to protein modification of PTP and due to alteration in PTP expression.