ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Signaling
This article is part of the Research TopicAntioxidants in Mitigating Oxidative Stress-Induced DamageView all 7 articles
CLIC1 and CLIC4 Demonstrate Cell Protective Antioxidant Activity Against UV Exposure
Provisionally accepted
- University of Technology Sydney School of Life Sciences, Broadway, Australia
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Redox-homeostasis is critical in maintaining healthy biological systems. Under physiological conditions, the human antioxidant defence system includes enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). We have recently shown that the Chloride Intracellular Ion Channel (CLIC) protein family, particularly CLIC1 and CLIC4, exhibit similar antioxidant cell protective activity. Our interest in the CLIC proteins' antioxidant capabilities has come from both their in vitro demonstrated oxidoreductase activities, and in-situ cell studies demonstrating that over-expression of these proteins afforded cell protection, while their knockdown led to increased cell susceptibility to oxidative assault. We were the first to demonstrate that exogenous addition of purified recombinant CLIC (rCLIC) proteins to skin cells provided cellular protection against H2O2-induced oxidative damage and led to reduced ROS production. The current in vitro study explores the cellular protective capabilities of two CLIC proteins against damage by UV irradiation of human skin cells. In addition, their cellular protective and antioxidant activities were compared to those of the well-known endogenous antioxidant proteins, glutaredoxin (Grx) and Glutathione S-transferase-Omega (GST-Ω) and the antioxidant drug, N-acetylcysteine (NAC). Comparison of CLIC1 or CLIC4 knockdown cells to rCLIC1 or rCLIC4 treated cells, provided further insights into the cellular protective and antioxidant capabilities of this family of Chloride Intracellular Ion Channel proteins, thereby opening new opportunities for novel therapeutic applications of these proteins.
Keywords: chloride intracellular ion channel (CLIC) proteins, CLIC1, CLIC4, fibroblast cells, Keratinocyte cells, antioxidant, oxidoreductase activity, UV irradiation
Received: 28 Jul 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Hossain, Alghalayini, Turkewitz and Valenzuela. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Stella M Valenzuela, stella.valenzuela@uts.edu.au
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