Abstract
BackgroundCadmium (Cd) is a well known environmental and industrial toxicant causing damaging effects in numerous organs. In this study, we examined the role of heme oxygenase-1 (HO-1) in modulating the Cd-induced apoptosis in human hepatoma (HepG2) cells after 24 h exposure.MethodsHepG2 cells were exposed to 5 and 10 μM Cd as CdCl2 for 24 h while other sets of cells were pre-treated with either 10 μM Cobalt protoporphyrin (CoPPIX) or 10 μM Tin protoporphyrin (SnPPIX) for 24 h, or 50 μM Z-DEVD-FMK for 1 h before exposure to 5 and 10 μM CdCl2 for 24 h. Expressions of caspase 3, cytosolic cytochrome c, mitochondrial Bax and anti-apoptotic BCL-xl proteins were assessed by western blot. Intracellular reactive oxygen species (ROS) production was determined using the dihydrofluorescein diacetate (H2DFA) method. Cell viability was assessed by MTT assay, while a flow cytometry method was used to assess the level of apoptosis in the cell populations.ResultsOur results show that there were a significant increase in the expression of cytosolic cytochrome c, mitochondrial Bax protein, and caspase 3 at 5 and 10 μM compared to the control, but these increases were attenuated by the presence of CoPPIX. The presence of SnPPIX significantly enhanced Cd-induced caspase 3 activities. CoPPIX significantly decreased the level of ROS production by 24.6 and 22.2 % in 5 and 10 μM CdCl2, respectively, but SnPPIX caused a significant increase in ROS production in the presence of CdCl2. HepG2 cell viability was also significantly impaired by 13.89 and 32.53 % in the presence of 5 and 10 μM CdCl2, respectively, but the presence of CoPPIX and Z-DEVD-FMK significantly enhanced cell survival, while SnPPIX enhanced Cd-impaired cell viability. The presence of CoPPIX and Z-DEVD-FMK also significantly decreased the population of apoptotic and necrotic cells compared with Cd.ConclusionIn summary, the present study showed that HO-1 attenuates the Cd-induced caspase 3 dependent pathway of apoptosis in HepG2 cells, probably by modulating Cd-induced oxidative stress.
Highlights
Cadmium (Cd) is a well known environmental and industrial toxicant causing damaging effects in numerous organs
We investigated whether Cd can activate the caspase 3-dependent pathway under our experimental conditions using HepG2 cells exposed to 5 and 10 μM CdCl2 for 24 h
To further confirm the involvement of the caspase 3dependent apoptotic pathway in HepG2 cells after Cd exposure, we examined the expression levels of mitochondrial BCL-xl, an anti-apoptotic protein, after Cd exposure
Summary
Cadmium (Cd) is a well known environmental and industrial toxicant causing damaging effects in numerous organs. Cadmium (Cd) has been referred to as a group 1 carcinogen and a potential human carcinogen with an estimated half-life of 15 to 20 years [1, 2] This implies that the metal escapes detoxification processes and makes it a more potent toxicant in the body. It is an environmental and industrial toxicant inducing multi-organ damaging effects. It is not naturally abundant and does not degrade in the environment causing a constant increasing risk of human exposure [3,4,5]. Studies have implicated the generation of reactive oxygen species (ROS) as an important mechanism in Cdinduced toxicity [17,18,19]
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