Work

Antioxidant-induced autophagy ameliorates oxidative mediated endoplasmic reticulum stress in ultraviolet-B-exposed human primary dermal fibroblasts

Year: 2025

Type: article

Abstract: Exposure to ultraviolet-B (UVB) radiation is a major contributor to skin damage and photoaging. UVB primarily induces oxidative stress and endoplasmic reticulum (ER) stress, leading to DNA instability and cellular dysfunction. Elevated reactive oxygen species (ROS) levels disrupt cellular homeostasis and activate stress-response pathways that exacerbate damage. While the effects of UVB-induced stress are well documented, strategies that enhance antioxidant defenses to simultaneously mitigate oxidative and ER stress while promoting cellular repair mechanisms, such as autophagy, remain underexplored. In this study, we investigated the protective role of antioxidant-mediated autophagy in UVB-exposed primary human dermal fibroblasts (HDFs). Our results show that UVB irradiation markedly increases ROS accumulation, triggering ER stress and DNA damage, ultimately impairing cell viability. Pharmacological enhancement of antioxidant defenses using Trolox, a vitamin E analog (α-tocopherol), effectively reduced ROS levels, alleviated oxidative and ER stress markers, and restored cellular homeostasis. Importantly, this intervention also activated autophagy, revealing a synergistic mechanism by which antioxidant and autophagic responses cooperate to protect cells. These findings establish a mechanistic link between autophagy activation and the alleviation of oxidative stress–induced ER stress, highlighting a coordinated cellular defense that mitigates DNA damage in HDFs. Collectively, our study provides valuable insights into potential therapeutic strategies aimed at enhancing skin resilience and protecting against UVB-induced damage. Augmenting antioxidant response improves autophagy signaling and protects from oxidative stress-mediated ER stress response in UVB-exposed HDFs. The black color indicates the effect of UVB. The green color indicates the effect of Trolox and/or Salubrinal. →Indicates activation. ⊣Indicates inhibition. • UVB exposure increases ROS, triggering ER stress and DNA damage in HDFs. • Trolox reduces ROS, alleviates stress markers, and restores cellular homeostasis. • Antioxidant treatment activates autophagy, enhancing cellular defense mechanisms. • Autophagy and antioxidant response synergistically mitigate oxidative DNA damage. • Findings suggest therapeutic strategies to enhance skin resilience against UVB exposure.

Source: Experimental Gerontology

DOI: 10.1016/j.exger.2025.112922

Authors: Sheikh Umar Ahmad, Aalim Maqsood Bhat, Gupta Ragni, Malik Ahmad Mushtaq, Sheikh Tasduq Abdullah

Institutions: Indian Institute of Integrative Medicine, Council of Scientific and Industrial Research, Academy of Scientific and Innovative Research

Language: English

Topic: Skin Protection and Aging

Subfield: Dermatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,400