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

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 - mM, in most of previous studies are higher than the IC50 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 ^M - 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.