Role of Hydrogen Sulfide, Biologically-Active Compound, During Cell De-Differentiation and Differentiation Processes

Ken Yaegaki*

Received: March 29, 2018;   Published: April 09, 2018

DOI: 10.26717/BJSTR.2018.03.000934

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Abstract

H₂S has been shown to act as a biologically active compound in mammalian cells; H₂S may also involve cardio protective or cardiovascular therapeutic effects. The concentrations of NaHS, used instead of H₂S at μM - mM, in most of previous studies are higher than the ₅₀ or Ki of cytochrome c oxidase (COX) activity by H₂S. However we found COX is inhibited by only 500 nM H₂S, reactive oxygen species causing DNA double-strand breaks are produced, and the mitochondrial membrane is depolarized. Following the above redox reactions, the p53 pathway is activated. Consequently, apoptosis is initiated. If the lowest concentration of H₂S (1 nM) is applied for hepatic or pancreatic differentiation from human-tooth pulp, the differentiation or proliferation is heavily promoted through WNT signaling and PI3K-AKT signaling pathways. A possibility of regenerative medicine or reversal ageing using H₂S at nM level is also suggested. On the other hand previous studies clearly indicated that the accuracy of dose-response studies using NaHS or Na₂S at μM - mM are questionable, we cannot produce constant concentration of H₂S using NaHS. NaHS is easily vaporized, and the dissociation constant of H₂S is not equal to that of NaHS. This presents a huge discrepancy affecting investigations of redox biology. The concentration of H₂S used for in vitro or in vivo experiments is strongly recommended to be determined by a precise and suitable measure. The review focuses on effects of H₂S on apoptosis, typical de-differentiation process, differentiation of the stem cells, and regenerative medicine.

Keywords: Hydrogen sulfide; Biologically-active compound; Reactive oxygen species; Apoptosis; Stem cell; Tooth

Abbreviations: H₂S: Hydrogen Sulfide; COX: Cytochrome C-Oxidase; MDA: Malon-di-Aldehyde; ROS: Reactive Oxygen Species; CBS: Cystathionine β-Synthase ; CSE: Cystathionine γ-Lyase; DCFH-DA: Di-Chloro-Fluorescein Diacetate; HGF: Human Gingival Fibroblasts; Caspase: Cysteinyl- Aspartic-Acid-Proteases; NO: Nitric Oxide; CO:Carbon Monoxide; MAPK: Mitogen-Activated Protein Kinase; ERK: Extracellular Signal-Regulated Kinase ; IPS: Induced Pluripotent Stem; ES: Embryonic Stem

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