Monomethylarsonous Acid, But Not Inorganic Arsenic, is a Mitochondria-Specific Toxicant in Vascular Smooth Muscle Cells
| Autor: | Tania Das Banerjee, Ruben K. Dagda, Barrett M. Welch, Roxana Khalili, Jeff E. Angermann, Clare Pace |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Vascular smooth muscle Cellular respiration Cell Survival Cell Respiration Myocytes Smooth Muscle Mitochondrion Biology Toxicology medicine.disease_cause Article Arsenic Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Adenosine Triphosphate Superoxides Internal medicine medicine Organometallic Compounds Animals Glycolysis Aorta Superoxide food and beverages General Medicine medicine.disease Mitochondria Rats Mitochondrial toxicity 030104 developmental biology Endocrinology Biochemistry chemistry Catalase 030220 oncology & carcinogenesis biology.protein Oxidative stress |
| Popis: | Arsenic exposure has been implicated as a risk factor for cardiovascular diseases, metabolic disorders, and cancer, yet the role mitochondrial dysfunction plays in the cellular mechanisms of pathology is largely unknown. To investigate arsenic-induced mitochondrial dysfunction in vascular smooth muscle cells (VSMCs), we exposed rat aortic smooth muscle cells (A7r5) to inorganic arsenic (iAs(III)) and its metabolite monomethylarsonous acid (MMA(III)) and compared their effects on mitochondrial function and oxidative stress. Our results indicate that MMA(III) is significantly more toxic to mitochondria than iAs(III). Exposure of VSMCs to MMA(III), but not iAs(III), significantly decreased basal and maximal oxygen consumption rates and concomitantly increased compensatory extracellular acidification rates, a proxy for glycolysis. Treatment with MMA(III) significantly increased hydrogen peroxide and superoxide levels compared to iAs(III). Exposure to MMA(III) resulted in significant decreases in mitochondrial ATP, aberrant perinuclear clustering of mitochondria, and decreased mitochondrial content. Mechanistically, we observed that mitochondrial superoxide and hydrogen peroxide contribute to mitochondrial toxicity, as treatment of cells with MnTBAP (a mitochondrial superoxide dismutase mimetic) and catalase significantly reduced mitochondrial respiration deficits and cell death induced by both arsenic compounds. Overall, our data demonstrates that MMA(III) is a mitochondria-specific toxicant that elevates mitochondrial and non-mitochondrial sources of ROS. |
| Databáze: | OpenAIRE |
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