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

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

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalMicrocirculation
Volume23
Issue number3
DOIs
Publication statusPublished - 2016

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Carbon Monoxide
Blood Vessels
Neoplasms
Gasotransmitters
Hemeproteins
Pentose Phosphate Pathway
Hepatic Stellate Cells
Vasoconstrictor Agents
Glycolysis
Enzymes
Microcirculation
Biotransformation
Heme
NADP
Vasodilation
Astrocytes
Methylation
Glutathione
Gases
Glucose

Keywords

  • cancer
  • chemoresistance
  • CO
  • cystathionine β-synthase
  • glutathione
  • soluble guanylate cyclase

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

CO-CBS-H2S Axis : From Vascular Mediator to Cancer Regulator. / Suematsu, Makoto; Nakamura, Takashi; Tokumoto, Yasuhito; Yamamoto, Takehiro; Kajimura, Mayumi; Kabe, Yasuaki.

In: Microcirculation, Vol. 23, No. 3, 2016, p. 183-190.

Research output: Contribution to journalReview article

Suematsu, Makoto ; Nakamura, Takashi ; Tokumoto, Yasuhito ; Yamamoto, Takehiro ; Kajimura, Mayumi ; Kabe, Yasuaki. / CO-CBS-H2S Axis : From Vascular Mediator to Cancer Regulator. In: Microcirculation. 2016 ; Vol. 23, No. 3. pp. 183-190.
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