Abstract

In the present investigation, the toxicity of mercuric chloride (HgCl2) was evaluated in adult oval cells isolated from rat utilizing the 2-acetylaminofluorene/partial hepatectomy technique. Isolated oval cells were incubated with 5 μM of HgCl2 for 8 hr to elucidate in vitro cytotoxic responses. Recently, autophagic cell death was found in rat hepatocytes in vitro within 30 min of incubation with 5 μM of mercury (Hg) which triggered apoptosis and necroptosis in a time-dependent manner. Nuclear degradation occurred within 30 min of incubation and progressed with time until 8 hr. Apoptosis evidenced by activation of caspase-dependent pathway between 30 min to 8 hr of incubation was mediated via interchange of death domain signaling pathways. Receptor-interacting protein played a positive role to modulate the death domain receptors in the scenario of apoptotic death of oval cells until 6 hr. Autophagic marker proteins ATG12 and LC3B exerted a significant role in triggering apoptosis in 5 μM Hg-treated oval cells. No apparent expression of apoptosis-inducing-factor (AIF) and HMGB1 indicated absence of caspase-independent apoptosis and necrosis in the rat oval cells between 30 min and 8 hr. Thus a low concentration of Hg modulates programmed cell death in adult rat oval cells by altering expression of proteins involved in the molecular mechanisms of cellular functions.

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