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γ-Glutamylcysteine Alleviates t-BHP-Induced Oxidative Damage in NIH/3T3 Fibroblasts by Promoting Nuclear
Shuai Lu1, Yujie Pan2, Mingyan Xia3
1Department of Biology, School of Basic Medical Science Guizhou Medical University Guiyang China.
Abstract:
Fibroblasts are essential for tissue repair, but reactive oxygen species (ROS) can impair their function, leading to mitochondrial dysfunction and apoptosis. γ-Glutamylcysteine (γ-GC), a glutathione (GSH) precursor and potent antioxidant, may protect fibroblasts, though its mechanisms in ROS-mediated damage remain unclear. This study examined γ-GC's effects on tert-butyl hydroperoxide (t-BHP)-injured NIH/3T3 fibroblasts. γ-GC effectively reduced ROS levels, restored antioxidant defenses, and preserved mitochondrial function, thereby inhibiting apoptosis. Mechanistically, γ-GC upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and promoted its nuclear translocation. The Nrf2 inhibitor ML385 confirmed that γ-GC's protective effects were mediated through Nrf2 activation. These results demonstrate that γ-GC, as a direct GSH precursor, not only scavenges ROS but also enhances cellular antioxidant capacity and mitochondrial homeostasis. Its dual role in ROS mitigation and Nrf2 activation highlights γ-GC's therapeutic potential for improving aberrant tissue repair.
Insights
Gamma-glutamylcysteine (γ-GC), a glutathione precursor, protects fibroblasts from reactive oxygen species (ROS) damage by enhancing antioxidant defenses and mitochondrial function, highlighting its therapeutic potential.
Area of Science:
- Cell Biology
- Biochemistry
- Pharmacology
Background:
- Fibroblasts are crucial for tissue repair, but their function is compromised by reactive oxygen species (ROS).
- ROS-induced damage leads to mitochondrial dysfunction and apoptosis, impairing tissue healing.
- The protective mechanisms of glutathione (GSH) precursors like γ-glutamylcysteine (γ-GC) against ROS in fibroblasts are not fully understood.
Purpose of the Study:
- To investigate the protective effects of γ-glutamylcysteine (γ-GC) on fibroblasts injured by tert-butyl hydroperoxide (t-BHP).
- To elucidate the underlying mechanisms of γ-GC's action in mitigating ROS-mediated cellular damage.
- To assess γ-GC's potential therapeutic role in aberrant tissue repair.
Main Methods:
- NIH/3T3 fibroblasts were exposed to tert-butyl hydroperoxide (t-BHP) to induce oxidative stress.
- The effects of γ-glutamylcysteine (γ-GC) treatment on ROS levels, antioxidant defenses, mitochondrial function, and apoptosis were evaluated.
- Nuclear factor erythroid 2-related factor 2 (Nrf2) activation and nuclear translocation were assessed, with Nrf2 inhibition studies using ML385.
Main Results:
- γ-Glutamylcysteine (γ-GC) significantly reduced ROS levels and restored cellular antioxidant capacity in t-BHP-injured fibroblasts.
- γ-GC preserved mitochondrial function and inhibited apoptosis, demonstrating cytoprotective effects.
- γ-GC upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and promoted its nuclear translocation, with protective effects dependent on Nrf2 activation.
Conclusions:
- γ-Glutamylcysteine (γ-GC) acts as a direct glutathione precursor, effectively scavenging ROS and enhancing cellular antioxidant defenses.
- γ-GC promotes mitochondrial homeostasis and protects fibroblasts from oxidative stress via Nrf2 pathway activation.
- The dual action of ROS mitigation and Nrf2 activation positions γ-GC as a promising therapeutic agent for improving impaired tissue repair.
