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Updated: Aug 7, 2026
08:47
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Cadmium-induced apoptosis in rat hepatocytes does not necessarily involve caspase-dependent pathways
T N D Pham1, M Marion, F Denizeau
1Département de Chimie, Centre TOXEN, Université du Québec à Montréal, C.P. 8888, Succ. Centre-Ville, Montréal, Québec, Canada H3C 3P8.
Summary
Cadmium exposure induces apoptosis in rat liver cells via mitochondrial pathways. Early events involve cytochrome c and apoptosis-inducing factor release, independent of caspase signaling.
Area of Science:
- Hepatology
- Toxicology
- Cell Biology
Background:
- Cadmium (Cd) is a hepatotoxic environmental pollutant.
- Cd-induced liver cell apoptosis mechanisms require clarification.
- Oxidative stress is implicated in Cd toxicity.
Purpose of the Study:
- Investigate Cd-induced apoptosis in primary rat hepatocytes.
- Elucidate the molecular signaling pathways involved in Cd toxicity.
- Determine the role of caspases and mitochondrial pathways in Cd-induced apoptosis.
Main Methods:
- Primary rat hepatocyte cultures exposed to low Cd levels (1-5 microM) for short durations (6-12 h).
- Assessment of nuclear morphology, chromatin condensation, and DNA fragmentation.
- Measurement of caspase activities (caspase-9, -3, -8), cytochrome c release, and apoptosis-inducing factor (AIF) levels.
Main Results:
- Cd (1-5 microM) induced apoptosis in hepatocytes within 6-12 h.
- Increased caspase-9 and -3 activities were observed, with minimal caspase-8 activation.
- Significant release of cytochrome c and AIF into the cytosol indicated mitochondrial pathway involvement.
- Caspase inhibitors did not prevent Cd-induced apoptosis.
Conclusions:
- Cd induces time- and concentration-dependent apoptosis in rat hepatocytes.
- Early apoptotic events are mediated by mitochondrial pathways, including cytochrome c and AIF release.
- Caspase-dependent signaling plays a minor role in the initial stages of Cd-induced hepatocyte apoptosis.
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