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Heme oxygenase (HO)/CO protects cancer cells against oxidative stress, while the gas-responsive signaling mechanisms remain unknown.We have recently revealed that CO constitutively generated in brain inhibits H2S-producing cystathionine-synthase (CBS) and thereby regulate cerebral cortex microvessels tonically;the mechanisms contribute to hypoxic vasodilation, since hypoxia downregulates CO acutely to activate CBS in astrocytes, causing H2S-dependent microvascular dilatation.