Arsenite induces apoptosis in human mesenchymal stem cells by altering Bcl-2 family proteins and by activating intrinsic pathway

• Published in: Toxicology and applied pharmacology 2010-05, Vol.244 (3), p.263-272
• Main Authors: Yadav, Santosh, Shi, Yongli, Wang, Feng, Wang, He
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL CELLS; ANIMAL TISSUES; ANIMALS; Annexin V staining; APOPTOSIS; Apoptosis - drug effects; ARSENIC; ARSENIC COMPOUNDS; Arsenites - toxicity; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; BLOOD CIRCULATION; BODY; BONE MARROW; CARTILAGE; Caspase 3 - metabolism; Caspase 9 - metabolism; CELL CYCLE; Cell Cycle - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; CONNECTIVE TISSUE; DNA DAMAGES; ELEMENTS; ENVIRONMENTAL EXPOSURE; Environmental Pollutants - toxicity; G2-M arrest; Gene Expression - drug effects; HAZARDS; HEALTH HAZARDS; HEMATOPOIETIC SYSTEM; Human mesenchymal stem cells; Humans; MALES; MAMMALS; MAN; Medical sciences; MEN; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; MESSENGER-RNA; Metabolic Networks and Pathways; Metals and various inorganic compounds; MUSCLES; Nucleic Acid Synthesis Inhibitors - toxicity; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; Poly(ADP-ribose) Polymerases - metabolism; PRIMATES; PROTEINS; Proto-Oncogene Proteins c-bcl-2 - drug effects; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; PUBLIC HEALTH; RNA; RNA, Messenger - metabolism; S-phase; SEMIMETALS; SKELETON; SOMATIC CELLS; STEM CELLS; Toxicology; TUNEL; Up-Regulation - drug effects; VERTEBRATES
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2010.01.001

Purpose: Environmental exposure to arsenic is an important public health issue. The effects of arsenic on different tissues and organs have been intensively studied. However, the effects of arsenic on bone marrow mesenchymal stem cells (MSCs) have not been reported. This study is designed to investigate the cell death process caused by arsenite and its related underlying mechanisms on MSCs. The rationale is that absorbed arsenic in the blood circulation can reach to the bone marrow and may affect the cell survival of MSCs. Methods: MSCs of passage 1 were purchased from Tulane University, grown till 70% confluency level and plated according to the experimental requirements followed by treatment with arsenite at various concentrations and time points. Arsenite (iAs III) induced cytotoxic effects were confirmed by cell viability and cell cycle analysis. For the presence of canonic apoptosis markers; DNA damage, exposure of intramembrane phosphotidylserine, protein and m-RNA expression levels were analyzed. Results: iAs III induced growth inhibition, G2-M arrest and apoptotic cell death in MSCs, the apoptosis induced by iAs III in the cultured MSCs was, via altering Bcl-2 family proteins and by involving intrinsic pathway. Conclusion: iAs III can induce apoptosis in bone marrow-derived MSCs via Bcl-2 family proteins, regulating intrinsic apoptotic pathway. Due to the multipotency of MSC, acting as progenitor cells for a variety of connective tissues including bone, adipose, cartilage and muscle, these effects of arsenic may be important in assessing the health risk of the arsenic compounds and understanding the mechanisms of arsenic-induced harmful effects.