Role of Hydrogen Sulfide, Biologically-Active Compound, During Cell De-Differentiation and #DifferentiationProcesses by Ken Yaegaki in BJSTR

Abstract

H₂S has been shown to act as a #biologicallyactivecompound in #mammaliancells; 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 #redoxreactions, 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 #stemcells, and regenerative medicine.

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Role of Hydrogen Sulfide, Biologically-Active Compound, During Cell De-Differentiation and #DifferentiationProcesses by Ken Yaegaki in BJSTR