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Updated: May 18, 2026
An Anaerobic Biosensor Assay for the Detection of Mercury and Cadmium
Published on: December 17, 2018
Low concentration of mercury induces autophagic cell death in rat hepatocytes
Sarmishtha Chatterjee1, Atish Ray1, Sandip Mukherjee1
1Environmental Toxicology Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan, West Bengal, India.
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.
Insights
Low concentrations of mercury (5 µM mercuric chloride) induce autophagic cell death in rat hepatocytes. This non-apoptotic programmed cell death involves Atg5-Atg12 conjugation, modulated by damage-regulated autophagy modulator (DRAM) and p53.
Area of Science:
- Toxicology
- Cell Biology
- Molecular Biology
Background:
- Mercury compounds are known toxicants.
- Autophagy is a cellular degradation process crucial for homeostasis.
- Understanding mechanisms of mercury-induced cell death is vital.
Purpose of the Study:
- To investigate the induction of autophagy in rat hepatocytes by low concentrations of mercury.
- To determine the specific cell death pathway induced by mercuric chloride (HgCl2).
- To elucidate the molecular mechanisms underlying mercury-induced autophagy.
Main Methods:
- Hepatocytes were treated with varying doses of HgCl2 (1-10 µM) and time points (0-4 h).
- Autophagic cell death was assessed using monodansylcadaverine (MDC) staining.
- Apoptosis was evaluated by caspase 3 activation.
- Expression of Atg5-Atg12 conjugate, DRAM, and p53 was analyzed.
Main Results:
- Autophagic cell death was observed specifically at 5 µM HgCl2 within 30 minutes.
- Apoptosis, indicated by caspase 3 activation, occurred at 10 µM HgCl2.
- MDC-positive hepatocytes peaked at 1 hour.
- Atg5-Atg12 conjugation was triggered within 30 minutes and sustained for 4 hours.
- DRAM expression increased, while p53 levels decreased during mercury treatment.
Conclusions:
- Low concentration (5 µM) HgCl2 induces autophagy, a form of non-apoptotic programmed cell death, in rat hepatocytes.
- The process is initiated via Atg5-Atg12 covalent-conjugation.
- Damage-regulated autophagy modulator (DRAM) plays a role in modulating this pathway.
- The observed autophagy induction is dependent on p53.
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