Suppression of stress granule assembly by pyridoxal hydrochloride attenuates oxidative damage in skin fibroblasts

Abstract

Stress granules (SGs) are membrane-less cytoplasmic structures that form in response to various stress stimuli and play a critical role in maintaining cellular homeostasis. Dysregulation of SG dynamics has been implicated in several diseases, including neurodegenerative and inflammatory conditions; however, their role in skin biology remains largely unexplored. In this study, we identified pyridoxal hydrochloride, a form of vitamin B6, as a novel regulator of SG formation through a metabolite library screening. Our results demonstrate that pyridoxal hydrochloride significantly suppresses oxidative stress-induced SG formation in skin fibroblasts, exhibiting effects comparable to G3Ia, a known SG inhibitor. Furthermore, pyridoxal hydrochloride mitigates oxidative stress by reducing reactive oxygen species (ROS) accumulation and preventing cell toxicity. Notably, it also attenuates ROS-induced upregulation of MMP1, thereby preserving collagen1 stability. These findings suggest the crucial role of SGs in skin fibroblast homeostasis and suggest that pyridoxal hydrochloride may serve as a potential therapeutic agent for oxidative stress-related skin disorders.