title: Cadmium and α-lipoic acid activate similar de novo synthesis and recycling pathways for glutathione balance.
abstract: Glutathione (GSH) protects cells against oxidative stress. Redox modifiers induce GSH biosynthesis and recycling to maintain reduced environment inside cells. Cadmium (Cd2+) 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 Cd2+concentrations and ALA in HepG2 cells. ALA activates Nrf2 pathway leading to GSH increment. Pre-treatment with 1μM Cd2+or ALA produces tolerance to 5μM Cd2+toxic effects. 5μM Cd2+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 Cd2+pre-treatments. Exposure to low Cd2+concentration generate timely protective responses, similar to that elicited by ALA, maintaining a normal redox balance inside the cell due to GSH replenishment.
authors.affiliation: 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. Electronic address: josemacias@valles.udg.mx.
authors.forename: Jose
authors.initials: J
authors.lastname: Macias-Barragan
authors.affiliation: Department of Medical and Life Sciences, CUCienega, University of Guadalajara, 1115 Universidad Ave., Ocotlán, Jalisco, 47820, Mexico.
authors.forename: Selene G
authors.initials: SG
authors.lastname: Huerta-Olvera
authors.affiliation: Department of Microbiology and Pathology, CUCS, University of Guadalajara, 950 Sierra Mojada St., Guadalajara, Jalisco, 44340, Mexico.
authors.forename: Ivan
authors.initials: I
authors.lastname: Hernandez-Cañaveral
authors.affiliation: Laboratory of Immunology, Department of Physiology, CUCS, University of Guadalajara, 950 Sierra Mojada St., Guadalajara, Jalisco, 44340, Mexico.
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Pereira-Suarez
authors.affiliation: Laboratory of Immunology, Department of Physiology, CUCS, University of Guadalajara, 950 Sierra Mojada St., Guadalajara, Jalisco, 44340, Mexico.
authors.forename: Margarita
authors.initials: M
authors.lastname: Montoya-Buelna
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002104:Cadmium / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; C508600:IL6 protein, human; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D014409:Tumor Necrosis Factor-alpha; D002104:Cadmium; D008063:Thioctic Acid; D005978:Glutathione
keywords: -γ-GCL; Cadmium; GSR; Glutathione; Nrf2; α-Lipoic acid