Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective inhibition of neuronal and inducible nitric oxide synthase (NOS) with 2-iminobiotin previously showed a reduction in brain cell injury. In the present study, we investigated the effects of 2-iminobiotin treatment on insulin-like growth factor-1 (IGF-1) expression, caspase activity and cytokine expression in a newborn piglet model of perinatal hypoxia-ischaemia. Newborn piglets were subjected to 1 h of hypoxia-ischaemia and were treated intravenously with vehicle or 2-iminobiotin. Vehicle-treated piglets showed reduced IGF-1 mRNA expression and increased caspase-3 activity and DNA fragmentation. 2-Iminobiotin treatment, administered immediately upon reperfusion, prevented these observations. No differences in caspase-8 and -9 activity and cytokine [interleukin (IL)-1alpha/beta, IL-6, tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta] mRNA expression were demonstrated between vehicle- and 2-iminobiotin-treated piglets at 24 h following hypoxia-ischaemia. IGF-1 mRNA correlated inversely with caspase-3 and transferase-mediated dUTP-biotin in situ nick end labelling score in the cortex, but positively with caspase-8. Cytokine mRNA did not correlate with IGF-1 mRNA, caspase-3 activity or DNA fragmentation. The present results indicate that the previously demonstrated neuroprotective effect of 2-iminobiotin treatment after perinatal hypoxia-ischaemia coincided with a preservation of the endogenous IGF-1 production and reduced caspase-3 activity, but not with a significant decrease in cytokine production.
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PMID:Effects of selective nitric oxide synthase inhibition on IGF-1, caspases and cytokines in a newborn piglet model of perinatal hypoxia-ischaemia. 1264 Jan 78

We have shown earlier that 2-iminobiotin (2-IB) reduces hypoxia-ischemia (HI)-induced brain damage in neonatal rats, and presumed that inhibition of nitric oxide synthases (NOS) was the underlying mechanism. We now investigated the effect of 2-IB treatment in P7 rat pups to determine the role of gender and the neuroprotective mechanism. Pups were subjected to HI (occlusion of right carotid artery and 120 mins FiO(2) 0.08) and received subcutaneous (s.c.) 10 mg/kg 2-IB at 0, 12 and 24 h after hypoxia. After 6 weeks, neuronal damage was assessed histologically. We determined cerebral nitrite and nitrate (NO(x)) and nitrotyrosine, heat-shock protein 70, cytosolic cytochrome c, cleaved caspase 3, nuclear translocation of apoptosis-inducing factor (AIF) and the effect of 2-IB on NOS activity in cultured cells. 2-Iminobiotin treatment reduced long-term brain damage in female but not male rats. Unexpectedly, 2-IB treatment did not reduce cerebral NO(x) or nitrotyrosine levels, and did not inhibit NOS activity in vitro. The gender-dependent neuroprotective effect of 2-IB was reflected in inhibition of the HI-induced increase in cytosolic cytochrome c and cleaved caspase 3 in females only. Hypoxia-ischemia-induced activation of AIF was observed in males only and was not affected by 2-IB. Post-HI treatment with 2-IB provides gender-specific long- and short-term neuroprotection in female P7 rats via inhibition of the cytochrome c-caspase 3 neuronal death pathway. 2-Iminobiotin did not alter cerebral NO(x) nor inhibited NOS in intact cells. Therefore, we conclude that it is highly unlikely that the neuroprotective effect of 2-IB involves NOS inhibition.
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PMID:Gender-specific neuroprotection by 2-iminobiotin after hypoxia-ischemia in the neonatal rat via a nitric oxide independent pathway. 1673 41