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The mechanistic role of oxidative stress in cigarette smoke-induced cardiac stem cell dysfunction and prevention by ascorbic acid

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Abstract

Cigarette smoking causes a vast array of diseases including cardiovascular diseases. Our laboratory focuses on investigating cigarette smoke (CS)-induced cardiovascular malfunction and the responsible mechanisms utilizing the model, c-kit-positive cardiac stem cells (CSCs). The main objective of our study is to investigate whether CS extracts (CSEs) cause impairment of CSC functions via oxidative damage. We hypothesized that CSE, via oxidative modifications of CSC proteins and antioxidant enzymes, can modulate CSC functions and these modifications can be attenuated by ascorbate treatment. Our specific aims are (1) to investigate CSE-induced oxidative modification of CSC proteins via carbonylation, and prevention by ascorbic acid; (2) to investigate CSE-induced oxidative modification of antioxidant enzymes and ascorbic acid-mediated modulations; and (3) to investigate CSE-induced changes in CSC functions and protection by ascorbic acid. CSCs were cultured, and the aqueous extracts of CSE were prepared. CSE-induced modulations of CSC viability, oxidative modification of proteins, and antioxidant enzyme activities were detected using standard assays including Apostain, bromodeoxyuridine, and Oxiblot. CSE caused oxidative modification of CSC proteins, changed antioxidant enzyme levels, attenuated CSC proliferation, and accelerated CSC apoptosis. Ascorbic acid prevented CSE-induced CSC malfunctions, and ascorbic acid therapy might be useful in smoker CSC recipients and to condition CSCs prior to the transplant in the future. Cardiac stem cell therapy is currently undergoing in clinical trials.

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Abbreviations

CS:

Cigarette smoke

CSC:

Cardiac stem cell

CSCT:

Cardiac stem cell therapy

CSE:

Cigarette smoke extract

DNPH:

Dinitrophenylhydrazine

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Acknowledgements

We would like to thank Dr. Rokosh, Dr. Bolli, and Dr. Anversa for providing the c-kit+ cardiac stem cells.

Funding

We would like to acknowledge the Sullivan University System for providing the funding to Dr. Sumanasekera via faculty development grants RG_1_PS_2009 and RG_1_PS_2012-01.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Sullivan University College of Pharmacy, 2100 Gardiner Lane, Louisville, KY, 40205, USA

    Wasana K. Sumanasekera, Halle Thy Dao, Viktoria Shekhovtsova, Kadi Schultz, Mehul Jani, Felix Gyamfi, David M. Tran & Nolan Le

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  1. Wasana K. Sumanasekera
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  2. Halle Thy Dao
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Correspondence to Wasana K. Sumanasekera.

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Sumanasekera, W.K., Dao, H.T., Shekhovtsova, V. et al. The mechanistic role of oxidative stress in cigarette smoke-induced cardiac stem cell dysfunction and prevention by ascorbic acid. Cell Biol Toxicol 35, 111–127 (2019). https://doi.org/10.1007/s10565-018-9437-x

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