title: Low concentration of mercury induces autophagic cell death in rat hepatocytes.
abstract: In the present study, we attempted to elucidate the induction of autophagy in rat hepatocytes by a low concentration of mercury. Hepatocytes treated with different doses of mercuric chloride (HgCl2; 1, 2.5, 5 and 10 µM) and at different time intervals (0 min, 30 min, 1 h, 2 h and 4 h) show autophagic cell death only at 5 µM HgCl2 within 30 min of incubation. At 1 and 2.5 µM HgCl2, no cell death is recorded, while apoptosis is found at 10 µM HgCl2, as evidenced by the activation of caspase 3. Autophagic cell death is confirmed by the presence of monodansylcadaverine (MDC) positive hepatocytes which is found to be highest at 1 h. Atg5-Atg12 covalent-conjugation triggers the autophagic pathway within 30 min of 5 µM HgCl2 treatment and continues till 4 h of incubation. In addition, damage-regulated autophagy modulator (DRAM) expression gradually increases from 30 min to 4 h of treatment with mercury and a corresponding linear decrease in p53 has been observed. It is concluded that a low concentration (5 µM HgCl2) of mercury induces autophagy or nonapoptotic programmed cell death following an Atg5-Atg12 covalent-conjugation pathway, which is modulated by DRAM in a p53-dependent manner.
authors.affiliation: Environmental Toxicology Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan, West Bengal, India.
authors.forename: Sarmishtha
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Environmental Toxicology Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan, West Bengal, India.
authors.forename: Atish
authors.initials: A
authors.lastname: Ray
authors.affiliation: Environmental Toxicology Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan, West Bengal, India.
authors.forename: Sandip
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Environmental Toxicology Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan, West Bengal, India.
authors.forename: Soumik
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Molecular Endocrinology Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan, West Bengal, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kundu
authors.affiliation: Environmental Toxicology Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan, West Bengal, India shelleyb38@gmail.com.
authors.forename: Shelley
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001562:Benzimidazoles; D002478:Cells, Cultured; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004996:Ethidium; D005452:Fluoresceins; D022781:Hepatocytes / Q000187:drug effects*; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001562:Benzimidazoles; D004396:Coloring Agents; D005452:Fluoresceins; C447680:hoechst 32258; C093616:6-carboxyfluorescein diacetate; D008627:Mercuric Chloride; D004996:Ethidium