Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response
- PMID: 28163822
- PMCID: PMC5253485
- DOI: 10.1155/2017/9251303
Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response
Abstract
Arsenite is a known carcinogen and its exposure has been implicated in a variety of noncarcinogenic health concerns. Increased oxidative stress is thought to be the primary cause of arsenite toxicity and the toxic effect is thought to be linear with detrimental effects reported at all concentrations of arsenite. But the paradigm of linear dose response in arsenite toxicity is shifting. In the present study we demonstrate that arsenite effects on mitochondrial respiration in primary hepatocytes follow a nonlinear dose response. In vitro exposure of primary hepatocytes to an environmentally relevant, moderate level of arsenite results in increased oxidant production that appears to arise from changes in the expression and activity of respiratory Complex I of the mitochondrial proton circuit. In primary hepatocytes the excess oxidant production appears to elicit adaptive responses that promote resistance to oxidative stress and a propensity to increased proliferation. Taken together, these results suggest a nonlinear dose-response characteristic of arsenite with low-dose arsenite promoting adaptive responses in a process known as mitohormesis, with transient increase in ROS levels acting as transducers of arsenite-induced mitohormesis.
Conflict of interest statement
The authors declare that they have no conflict of interests.
Figures
Similar articles
-
Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension.Aging Cell. 2013 Jun;12(3):508-17. doi: 10.1111/acel.12076. Epub 2013 May 6. Aging Cell. 2013. PMID: 23534459 Free PMC article.
-
Dose and chemical species-specific effects of selenium against arsenite toxicity in cultured hepatocytes of rainbow trout (Oncorhynchus mykiss).Metallomics. 2017 Jun 21;9(6):744-756. doi: 10.1039/c7mt00006e. Metallomics. 2017. PMID: 28530295
-
A comparison of hepatocyte cytotoxic mechanisms for chromate and arsenite.Toxicology. 2005 Jan 31;206(3):449-60. doi: 10.1016/j.tox.2004.08.002. Toxicology. 2005. PMID: 15588934
-
Arsenite impinges on endoplasmic reticulum-mitochondria crosstalk to elicit mitochondrial ROS formation and downstream toxicity.Semin Cancer Biol. 2021 Nov;76:132-138. doi: 10.1016/j.semcancer.2021.06.002. Epub 2021 Jun 3. Semin Cancer Biol. 2021. PMID: 34089843 Review.
-
Calcium-dependent physiologic and pathologic stimulus-metabolic response coupling in hepatocytes.Cell Calcium. 2012 Jul;52(1):93-102. doi: 10.1016/j.ceca.2012.04.009. Epub 2012 May 6. Cell Calcium. 2012. PMID: 22564906 Free PMC article. Review.
Cited by
-
Exposure of Bladder Cancer Cells to Blue Light (λ = 453 nm) in the Presence of Riboflavin Synergistically Enhances the Cytotoxic Efficiency of Gemcitabine.Int J Mol Sci. 2024 Apr 29;25(9):4868. doi: 10.3390/ijms25094868. Int J Mol Sci. 2024. PMID: 38732087 Free PMC article.
-
Proteomic-miRNA Biomics Profile Reveals 2D Cultures of Human iPSC-Derived Neural Progenitor Cells More Sensitive than 3D Spheroid System Against the Experimental Exposure to Arsenic.Mol Neurobiol. 2024 Aug;61(8):5754-5770. doi: 10.1007/s12035-024-03924-z. Epub 2024 Jan 16. Mol Neurobiol. 2024. PMID: 38228842
-
Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria.Int J Mol Sci. 2023 Sep 22;24(19):14459. doi: 10.3390/ijms241914459. Int J Mol Sci. 2023. PMID: 37833908 Free PMC article. Review.
-
Mitochondria in the Spotlight: C. elegans as a Model Organism to Evaluate Xenobiotic-Induced Dysfunction.Cells. 2023 Aug 22;12(17):2124. doi: 10.3390/cells12172124. Cells. 2023. PMID: 37681856 Free PMC article. Review.
-
Effects of Sodium Arsenite on the Myocardial Differentiation in Mouse Embryonic Bodies.Toxics. 2023 Feb 1;11(2):142. doi: 10.3390/toxics11020142. Toxics. 2023. PMID: 36851018 Free PMC article.
References
-
- World-Health-Organisation. Environmental Health Criteria. WHO; 2004. Arsenic and arsenic compounds beds.
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources