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

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2

초록

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.

키워드

Pyridoxal hydrochloride; Stress granules; MMP1; Collagen1; Skin fibroblasts; HYDROGEN-PEROXIDE; MATRIX METALLOPROTEINASES; INITIATION
제목
Suppression of stress granule assembly by pyridoxal hydrochloride attenuates oxidative damage in skin fibroblasts
저자
Kim, Seong Hyun; Kim, Yong Hwan; Kim, Joon Bum; Park, Na Yeon; So, Jun Hee; Park, Daeun; Choi, Dong Kyu; Yeom, Eunbyul; Gwon, Youngdae; Jo, Doo Sin; Lee, Jin-A; Bae, Ji-Eun; Cho, Dong-Hyung
DOI
10.1016/j.bmcl.2025.130238
발행일
2025-08-01
유형
Article
저널명
Bioorganic & Medicinal Chemistry Letters
권
123