Soluble guanylyl cyclase (sGC) is the principal enzyme in mediating the biological actions of nitric oxide. On activation, sGC converts guanosine triphosphate to guanosine 3',5'-cyclic monophosphate (cGMP), which mediates diverse physiological processes including vasodilation, platelet aggregation, and myocardial functions predominantly by acting on cGMP-dependent protein kinases[1].Impaired NO-sGC-cGMP signaling could lead to osteoblast apoptosis by mechanisms involving the oxidative-stress-induced shift of the redox state of the reduced heme to oxidized sGC, leading to diminished heme binding to the enzyme and rendering the sGC unresponsive to NO. Targeting oxidized sGC to enhance cGMP production could restore proliferation and differentiation of osteoblasts into osteocytes[2]. ODQ is a potent and selective sGC inhibitor. ODQ enhances the pro-apoptotic effects of Cisplatin in human mesothelioma cells. At 30 and 50 μM, ODQ causes significant induction of apoptosis in the NCI-H2452 cells, elevating apoptotic levels by 12 fold and 15 fold, respectively. At 10μM, a concentration below the threshold for induction of apoptosis by ODQ, ODQ in combination with Cisplatin enhanced (in fact, doubled) the pro-apoptotic effects of Cisplatin at 1 μM[3]. ODQ (2 mg/kg; i.p.) reduces the multiple organ injury and dysfunction caused by wall fragments of Gram-positive or Gram-negative bacteria in the anesthetized rat[4].
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