CO-CBS-H2S Axis: From Vascular Mediator to Cancer Regulator

Makoto Suematsu, Takashi Nakamura, Yasuhito Tokumoto, Takehiro Yamamoto, Mayumi Kajimura, Yasuaki Kabe

研究成果: Review article査読

17 被引用数 (Scopus)


CO is a gaseous mediator generated by HO. Our previous studies revealed that CO generated from inducible HO-1 or from constitutive HO-2 modulates function of different heme proteins or enzymes through binding to their prosthetic ferrous heme to alter their structures, regulating biological function of cells and organs. Such CO-directed target macromolecules include sGC and CBS. In the liver, CO serves as a sinusoidal dilator through its action on sGC in hepatic stellate cells, while the same gas accounts for vasoconstrictor that inhibits H2S generated by CO-sensitive CBS in astrocytes. Since molecular O2 is a substrate for HO, the latter mechanism contributes to hypoxic vasodilation in neurovascular units. We have recently uncovered that stress-inducible CO in and around cancer cells suppresses CBS to result in decreased methylation of PFKFB3, the enzyme regulating PFK-1, leading to a shift of glucose biotransformation from glycolysis toward pentose phosphate pathway; such a metabolic remodeling causes chemoresistance through increasing NADPH and reduced glutathione under stress conditions for cancer cells. This article reviews the intriguing networks of CO-sensitive metabolic regulatory mechanisms in microcirculation and cancer.

出版ステータスPublished - 2016

ASJC Scopus subject areas

  • 生理学
  • 分子生物学
  • 循環器および心血管医学
  • 生理学(医学)


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