Macias-Barragan Jose, Huerta-Olvera Selene G, Hernandez-Cañaveral Ivan, Pereira-Suarez Ana Laura, Montoya-Buelna Margarita
Department of Health Sciences, CUValles, University of Guadalajara, Guadalajara - Ameca Rd Km. 45.5, Ameca, Jalisco, 46600, Mexico; Laboratory of Immunology, Department of Physiology, CUCS, University of Guadalajara, 950 Sierra Mojada St., Guadalajara, Jalisco, 44340, Mexico.
Department of Medical and Life Sciences, CUCienega, University of Guadalajara, 1115 Universidad Ave., Ocotlán, Jalisco, 47820, Mexico.
Environ Toxicol Pharmacol. 2017 Jun;52:38-46. doi: 10.1016/j.etap.2017.03.007. Epub 2017 Mar 9.
Glutathione (GSH) protects cells against oxidative stress. Redox modifiers induce GSH biosynthesis and recycling to maintain reduced environment inside cells. Cadmium (Cd) is a heavy metal that activates redox-sensitive transcriptional factors. The antioxidant α-lipoic acid (ALA) has shown to modulate GSH pathways. This study aimed to investigate de novo synthesis and recycling pathways for GSH balance by different Cd concentrations and ALA in HepG2 cells. ALA activates Nrf2 pathway leading to GSH increment. Pre-treatment with 1μM Cd or ALA produces tolerance to 5μM Cd toxic effects. 5μM Cd exposure significantly augmented nuclear Nrf2, GSH and GCLC, GCLM, HMOX1, TNFα and IL-6 mRNA expression but not GSR, however these upsurges were significantly abrogated by ALA or 1μM Cd pre-treatments. Exposure to low Cd concentration generate timely protective responses, similar to that elicited by ALA, maintaining a normal redox balance inside the cell due to GSH replenishment.
谷胱甘肽（GSH）可保护细胞免受氧化应激。氧化还原调节剂可诱导GSH的生物合成和循环利用，以维持细胞内的还原环境。镉（Cd）是一种重金属，可激活氧化还原敏感的转录因子。抗氧化剂α-硫辛酸（ALA）已被证明可调节GSH途径。本研究旨在探讨不同Cd浓度和ALA对HepG2细胞中GSH平衡的从头合成和循环途径的影响。ALA激活Nrf2途径导致GSH增加。用1μM Cd或ALA预处理可产生对5μM Cd毒性作用的耐受性。5μM Cd暴露显著增加了细胞核Nrf2、GSH以及GCLC、GCLM、HMOX1、TNFα和IL-6 mRNA的表达，但未增加GSR的表达，然而，这些增加被ALA或1μM Cd预处理显著消除。暴露于低Cd浓度会产生及时的保护反应，类似于ALA引发的反应，由于GSH的补充，维持细胞内正常的氧化还原平衡。
