Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of coptisine against oxidative stress-induced DNA damage and apoptosis in HaCaT keratinocytes

Rok, strany: 2019, 281 - 294

In this study, the protective effect of coptisine on the oxidative damage-mediated apoptosis was evaluated in cultured human HaCaT keratinocytes. The results demonstrate that preincubation of cells with coptisine prior to H2O2 stimulation resulted in significant inhibition of cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. Coptisine also restored H2O2-induced mitochondrial dysfunction and decrease of ATP production, and prevented apoptosis by inhibiting Bax/Bcl-2 ratio, caspase-3 activity, and poly(ADP-ribose) polymerase degradation. Interestingly, the expressions of nuclear factor-erythroid-2-related factor 2 (Nrf2) and its active form, phosphorylated Nrf2, were strikingly promoted by coptisine in the presence of H2O2, which was associated with a marked increase in the expression of heme oxygenase-1 (HO-1). However, coptisine-induced HO-1 expression was completely abrogated by Nrf2-specific small interfering RNA (Nrf2-siRNA), which suggests that the increased expression of HO-1 by coptisine is Nrf2-dependent. In addition, Nrf2-siRNA transfection significantly eliminated the protective effect of coptisine on H2O2-induced cytotoxicity, and this effect was similar to that by zinc protoporphyrin IX (ZnPP), an HO-1 specific inhibitor. Furthermore, the protective effects of coptisine against H2O2-induced cytotoxicity were abolished by ZnPP, indicating that coptisine protects keratinocytes against oxidative stress-induced injury through activation of the Nrf2/HO-1 signaling pathway.

ISO 690:

Choi, Y. 2019. Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of coptisine against oxidative stress-induced DNA damage and apoptosis in HaCaT keratinocytes. In General Physiology and Biophysics, vol. 38, no.4, pp. 281-294. 0231-5882.

APA:

Choi, Y. (2019). Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of coptisine against oxidative stress-induced DNA damage and apoptosis in HaCaT keratinocytes. General Physiology and Biophysics, 38(4), 281-294. 0231-5882.