Activation of the ERK/Creb/Bcl‑2 pathway protects periodontal ligament stem cells against hydrogen peroxide‑induced oxidative stress

Abstract

Periodontal ligament stem cells (PDLSCs) are promising stem cells sources for regenerative medicine, particularly clinical periodontal ligament repair. It is critical to maintain high quality and a large quantity of PDLSCs for clinical usage. However, how PDLSCs respond to environmental stimuli, including reactive oxygen species (ROS), is poorly understood. The aim of the present study was to investigate how PDLSCs react to oxidative stress and the underlying mechanisms. Hydrogen peroxide-induced oxidative stress was used to mimic a ROS increase in rat PDLSCs. The expression levels of Creb were detected under oxidative stress to examine the role that Creb serves in PDLSCs under oxidative stress. The present results demonstrated that the expression of Creb was reduced in a dose-dependent manner in response to the H 2 O 2 stimulus. Overexpressing Creb significantly reduced the ROS levels and protein expression levels of apoptotic genes in PDLSCs. The phosphorylation of the ERK pathway is indispensable in the activation of Creb-induced protection. Our results revealed a protective role of Creb in ROS-induced apoptosis, and validated the ERK/Creb/apoptosis regulator Bcl-2 pathway works as an anti-apoptotic signaling in PDLSCs. These findings will facilitate the in vitro culturing of PDLSCs for clinical usage and promote stem cell based therapy for periodontal tissue regeneration.

Klotho inhibits H2O2‐induced oxidative stress and apoptosis in periodontal ligament stem cells by regulating UCP2 expression

“…PDLSCs were treated with H 2 O 2 (100 μmol/L) to induce oxidative stress. Previous research has confirmed that H 2 O 2 (100–500 μmol/L) is cytotoxic and promotes cell apoptosis in PDLSCs 26 . The present study further showed that H 2 O 2 treatment decreased klotho and UCP2 levels.…”

Erianthridin Induces Non-small Cell Lung Cancer Cell Apoptosis through the Suppression of Extracellular Signal-regulated Kinase Activity

“…Notably, the levels of anti-apoptotic and pro-apoptotic proteins in the Bcl-2 family were directly regulated by ERK signaling through their transcriptional and posttranslational mechanisms. Bcl-2 transcription mediated by the Creb pathway is driven by ERK activation [38,39], and Bcl-2 is phosphorylated stably by ERK [40]. An ERK inhibitor was shown to induce apoptosis by increasing Bax levels and abolishing Bcl-2 levels [41], a result consistent with our finding that ERK inhibition by U0126 enhances apoptotic induction by ETD and enhances the ratio of Bax/Bcl-2.…”

Chronic exposure of ErbB TKIs inhibits DRA expression and activity through an ERK/Elk-1/CREB/AP-1 dependent pathway

“…However, we observed a proportional reduction in both total and phosphorylated CREB by ErbB TKIs and the ERK inhibitor SCH772984, implicating that with chronic ErbB TKI treatment, the role of phosphorylated ERK involves maintaining CREB expression and phosphorylation, and this occurs at a post-translational level, given the unchanged CREB mRNA level, although the mechanism has not been determined. Notably, other publications did not observe a similar effect of ERK inhibitors on CREB expression (Fu et al, 2019;Li et al, 2018), a discrepancy which might be explained by the shorter period (maximum 24 hours) of exposure in those studies as compared to ours (6 days).…”