Resveratrol protects UVB‐irradiated keratinocytes by upregulating HO‐1 expression and improving mitochondrial function via endogenous CO signaling

Abstract

Excessive exposure to ultraviolet (UV) radiation has been reported to promote uncontrolled reactive oxygen species (ROS) production, particularly in the mitochondria, and thus implicated in the prevalence of skin injuries. Considering the antioxidative effect of resveratrol (RES) in reducing UV‐induced ROS production in human keratinocytes (HaCaT cells) and the role of carbon monoxide (CO) in regulating oxidative stress, we hypothesized that RES may promote cellular antioxidant response by activating heme oxygenase‐1 (HO‐1) which can generate its enzymatic product, CO, in UVB‐irradiated keratinocytes. To test our hypothesis, we treated HaCaT cells with CO‐releasing molecule 2 (CORM‐2) (source of CO) and RES either independently or in combination and irradiated the cells with UVB. Co‐treatment of CO with RES upregulated HO‐1 expression and subsequently reduced intracellular ROS in response to UV irradiation. Moreover, UVB treatment alone induced mitochondrial biogenesis, but treatment with CO and RES did not increase it further. With UVB treatment, RES showed enhanced mitochondrial respiration while CO did not instigate any effect; however, independent or co‐treatment mitigated mitochondrial ROS production. Taken together, our data support the impression that endogenous CO generated from RES‐mediated activation of HO‐1 may play a crucial role in cellular antioxidant response and mitochondrial function.Support or Funding InformationThis work was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries (IPET) through the High Value‐Added Food Technology Development Program, funded by the Ministry of Agriculture, Food, and Rural Affairs (Grant No. 116026‐03‐2‐HD020), Republic of Korea.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.