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Hexavalent chromium-induced apoptosis in Hep3B cells is accompanied by calcium overload, mitochondrial damage, and AIF translocation
- Source :
- Ecotoxicology and Environmental Safety, Vol 208, Iss, Pp 111391-(2021)
- Publication Year :
- 2020
-
Abstract
- Hexavalent chromium [Cr(VI)] is a pervasive environmental pollutant that can enter the body through a variety of routes and cause organ toxicity, genetic damage, and cancer. Cr(VI)-induced apoptosis is a toxicant mechanism of Cr(VI). Studies have shown that Cr(VI) can induce p53-independent apoptosis, but the mechanisms are not fully understood. The intracellular calcium concentration affects cellular life. Apoptosis-inducing factor (AIF), a caspase-independent apoptotic effector, can induce DNA degradation. Using p53-null Hep3B cells, we investigated the effects of cytoplasmic calcium homeostasis and AIF on Cr(VI)-induced apoptosis. We found that 20 µM of Cr(VI) induced DNA damage and mitochondrial permeability transition pore (MPTP) openings, causing calcium overload that was accompanied by decreased Ca2+-Mg2+-ATPase and Na+-K+-ATP activities, downregulation of calmodulin (CaM) and Ca2+/CaM-dependent protein kinase II (CAMKII) mRNA, and increased expression of p-CaMKII/CaMKII protein. After treatment with calcium chelating agent BAPTA-AM, Cr(VI)-induced DNA damage, calcium overload, and apoptosis were reduced. AIF was released from the mitochondria and translocated into the nuclei. As the Cr(VI) treatment time progressed, the mRNA and protein expression of B cell lymphoma 2 (Bcl-2) and heat-shock protein 70 (HSP70) decreased, whereas the mRNA and protein expression of Bcl-2-associated X (Bax), cyclophilin A (CypA), and endonuclease G (EndoG) were upregulated. These results indicated that Cr(VI)-induced apoptosis of Hep3B cells (p53-null) was closely associated with calcium overload, and was accompanied by the activation of Ca2+/CaM/CaMKII signaling pathway. Besides, Cr(VI) triggered AIF nuclear translocation in Hep3B cells, accompanied by the changes in the levels of apoptosis-associated factors. These results provide additional experimental evidence of the molecular mechanisms involved in Cr(VI)-induced p53-independent apoptosis.
- Subjects :
- Chromium
DNA damage
Health, Toxicology and Mutagenesis
Nuclear translocation
0211 other engineering and technologies
ENDOG
chemistry.chemical_element
Apoptosis
02 engineering and technology
Hexavalent chromium
010501 environmental sciences
Mitochondrion
Calcium
01 natural sciences
Environmental pollution
Calcium in biology
Hazardous Substances
Ca2+/calmodulin-dependent protein kinase
Humans
GE1-350
Calcium overload
Egtazic Acid
0105 earth and related environmental sciences
021110 strategic, defence & security studies
Mitochondrial damage
Cell Death
Chemistry
Public Health, Environmental and Occupational Health
Apoptosis Inducing Factor
General Medicine
Pollution
Cell biology
Mitochondria
Environmental sciences
TD172-193.5
Mitochondrial permeability transition pore
Reactive Oxygen Species
Signal Transduction
Subjects
Details
- ISSN :
- 10902414
- Volume :
- 208
- Database :
- OpenAIRE
- Journal :
- Ecotoxicology and environmental safety
- Accession number :
- edsair.doi.dedup.....0192f3e80d63e500cf93737cc5c6a525