Induction of Transient Cell Cycle Arrest by H2o2 Via Modulation of Ultradian Oscillations of Hes1, Socs3, and P-Stat3 in Fibroblast Cells Publisher Pubmed



Babaei Khalili M¹ ; Yazdanparast R¹ ; Nowrouzi A² Show Affiliations
Source: Journal of Cellular Biochemistry Published:2018

Abstract

Biological clocks, time-keeping systems, enable the living organisms to synchronize their biochemical processes with their environment. Among these molecular oscillators, ultradian oscillators have been identified with volatility less than 24 h. Transcription factor Hes1, a member of the basic Helix-loop-Helix (bHLH) protein family, has an oscillation duration of 2 h in vertebrates. Due to the pivotal role of oxidative stress in many human diseases, we evaluated the effect(s) of oxidative stress on Hes1 oscillator, its upstream regulators, and its downstream cell cycle regulators. NIH/3T3 mouse fibroblast cells were treated with sublethal (250 μM) and lethal (1000 μM) doses of H2O2 for 30 min. H2O2 generated a delay in p-Stat3 and Socs3 mRNAs followed by suppression of Hes1 protein. These events were accompanied by simultaneous upregulation of p21 and downregulation of cyclinD1, resulting in a temporary arrest of the cell cycle. In conclusion, the elimination of Hes1 protein oscillation by H2O2 may represent a defense mechanism against oxidative stress in fibroblast cells. © 2017 Wiley Periodicals, Inc.