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Caspase-Dependent and Caspase-Independent Pathways Are Involved in Cadmium-Induced Apoptosis in Primary Rat Proximal Tubular Cell Culture.
- Source :
-
PloS one [PLoS One] 2016 Nov 18; Vol. 11 (11), pp. e0166823. Date of Electronic Publication: 2016 Nov 18 (Print Publication: 2016). - Publication Year :
- 2016
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Abstract
- We designed this study to investigate whether cadmium induces caspase-independent apoptosis and to investigate the relationship between the caspase-dependent and caspase-independent apoptotic pathways. Cadmium (1.25-2.5 μM) induced oxidative stress in rat proximal tubular (rPT) cells, as seen in the reactive oxygen species levels; N-acetylcysteine prevented this. Cyclosporin A (CsA) prevented mitochondrial permeability transition pore opening and apoptosis; there was mitochondrial ultrastructural disruption, mitochondrial cytochrome c (cyt c) translocation to the cytoplasm, and subsequent caspase-9 and caspase-3 activation. Z-VAD-FMK prevented caspase-3 activation and apoptosis and decreased BNIP-3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) expression levels and apoptosis-inducing factor/endonuclease G (AIF/Endo G) translocation. Simultaneously, cadmium induced prominent BNIP-3 expression in the mitochondria and cytoplasmic AIF/Endo G translocation to the nucleus. BNIP-3 silencing significantly prevented AIF and Endo G translocation and decreased the apoptosis rate, cyt c release, and caspase-9 and caspase-3 activation. These results suggest that BNIP-3 is involved in the caspase-independent apoptotic pathway and is located upstream of AIF/Endo G; both the caspase-dependent and caspase-independent pathways are involved in cadmium-induced rPT cell apoptosis and act synergistically.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Caspase Inhibitors pharmacology
Cytochromes c metabolism
Endodeoxyribonucleases metabolism
Gene Silencing
Membrane Proteins genetics
Mitochondria drug effects
Mitochondria metabolism
Mitochondrial Membrane Transport Proteins metabolism
Mitochondrial Permeability Transition Pore
Mitochondrial Proteins genetics
Oxidative Stress drug effects
Primary Cell Culture
Rats
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Apoptosis drug effects
Cadmium pharmacology
Caspases metabolism
Epithelial Cells drug effects
Epithelial Cells metabolism
Kidney Tubules, Proximal drug effects
Kidney Tubules, Proximal metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27861627
- Full Text :
- https://doi.org/10.1371/journal.pone.0166823