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Environmentally Persistent Free Radicals Cause Apoptosis in HL-1 Cardiomyocytes

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Abstract

Samples of environmental particulate matter contain environmentally persistent free radicals (EPFRs) capable of sustained generation of oxygen radicals. While exposure to EPFRs produces cardiac toxicity and oxidative stress in experimental animals, the underlying mechanisms are largely unknown. To determine whether EPFRs could directly damage cardiomyocytes, cultured mouse cardiomyocytes (HL-1) and primary rat adult left ventricular myocytes (ALVM) were incubated with an EPFR consisting of 1,2-dichlorobenzene chemisorbed to CuO-coated silica beads (DCB230). Treatment with DCB230 killed both HL-1 and ALVM in a dose- and time-dependent manner. The cytotoxic effects of DCB230 were significantly attenuated by treatment with α-tocopherol. One to 2 h after exposure to DCB230, there were significant reductions in mitochondrial membrane potential and significant increases in cleaved caspase-9, but no significant increases in DNA damage or cell death. After 8 h of treatment, there were significant increases in caspase-3, caspase-9, DNA damage and PARP cleavage associated with significant cell death. Together, these data indicate that DCB230 kills HL-1 myocytes by inducing oxidative stress that initiates apoptosis, with the intrinsic or mitochondrial pathway acting early in the apoptotic signaling process.

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Acknowledgments

The authors would also like to thank Dr. Charles Nichols for this assistance with the confocal microscopy and Dr. Martin Ronis for his insights and editorial suggestions.

Funding

This work was supported by the National Institutes of Health P42ES013648 and P30GM106392 to K.J.V.

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Authors and Affiliations

  1. Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center New Orleans, 1901 Perdido St, MEB 5262, New Orleans, LA, USA

    Gin C. Chuang, Huijing Xia, Sarah E. Mahne & Kurt J. Varner

  2. Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center New Orleans, New Orleans, LA, USA

    Huijing Xia, Sarah E. Mahne & Kurt J. Varner

  3. Superfund Research Center, Louisiana State University, Baton Rouge, LA, USA

    Gin C. Chuang, Huijing Xia & Kurt J. Varner

Authors
  1. Gin C. Chuang
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  2. Huijing Xia
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Correspondence to Kurt J. Varner.

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Chuang, G.C., Xia, H., Mahne, S.E. et al. Environmentally Persistent Free Radicals Cause Apoptosis in HL-1 Cardiomyocytes. Cardiovasc Toxicol 17, 140–149 (2017). https://doi.org/10.1007/s12012-016-9367-x

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