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Oleic Acid Protects from Arsenic-Induced Cardiac Hypertrophy via AMPK/FoxO/NFATc3 Pathway

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Abstract

Arsenic toxicity is one of the major environmental problems causing various diseases, cardiovascular disorders is one of them. Several epidemiological studies have shown that arsenic causes cardiac hypertrophy but the detailed molecular mechanism is to be studied yet. This study is designed to determine the molecules involved in the augmentation of arsenic-induced cardiac hypertrophy. Furthermore, the effects of oleic acid on arsenic-induced hypertrophy and cardiac injury have also been investigated. Our results show that arsenic induces cardiac hypertrophy both in vivo in mice and in vitro in rat H9c2 cardiomyocytes. Moreover, arsenic results in decreased activity of AMPK and FoxO1 along with increased NFATc3 expression, a known cardiac hypertrophy inducer. In addition, activation of AMPK and FoxO1 results in reduced NFATc3 expression causing attenuation of arsenic-induced cardiac hypertrophy in H9c2 cells. Interestingly, we have observed that oleic acid helps in ameliorating cardiac hypertrophy in arsenic-exposed mice. Our studies on protection from arsenic-induced cardiac hypertrophy by oleic acid in H9c2 cells shows that oleic acid activates AMPK along with increased nuclear FoxO1 localization, thereby reducing NFATc3 expression and attenuating cardiomyocyte hypertrophy. This study will help in finding out new avenues in treating arsenic-induced cardiac hypertrophy.

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Abbreviations

AMPK:

Adenosine monophosphate-activated protein kinase

FoxO:

Forkhead box transcription factor

CVDs:

Cardiovascular-associated diseases

ROS:

Reactive oxygen species

OA:

Oleic acid

i.p.:

Intraperitoneal

ppm:

Parts per million

IAEC:

Institutional Animal Ethics Committee

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal Bovine serum

PBS:

Phosphate-buffered saline

PCR:

Polymerase chain reaction

PFA:

Paraformaldehyde

WGA:

Wheat germ agglutinin

BSA:

Bovine serum albumin

ANP:

Atrial natriuretic peptide

BNP:

Brain natriuretic peptide

S.E.:

Standard error

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Acknowledgements

We thank SC lab members for their kind support in the initial cell culture studies. We thank Dr. Amalesh Samanta, Department of Pharmaceutical Technology, Jadavpur University for his assistance in the animal study. All the authors read and approved the manuscript.

Funding

This work was supported by Department of Biotechnology sponsored Bio-CARe (BT/Bio-CARe/01/9686/2013-14) grant and Central University Grant Commission-Start Up Grant [No. F.4.5(192-FRP)/2015(BSR)] to AS and Central University Grant Commission-Major Research Project Grant (MRP-MAJOR-BIOT-2013-12885); Central Govt. of India, Ministry of Science and Technology, Department of Biotechnology sponsored project Grant (BT/PR11785/BRB/10/1324/2014) and Department of Science & technology (DST-SERB, No.: EMR/2017/001382) to SC.

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Authors and Affiliations

  1. Department of Life science and Biotechnology, Jadavpur University, 188, Raja S. C. Mallick Road, Kolkata, West Bengal, 700032, India

    Jayeeta Samanta, Arunima Mondal & Arunima Sengupta

  2. Department of Physics, Jadavpur University, Kolkata, India

    Srimoyee Saha

  3. Department of Life sciences, Presidency University, Kolkata, India

    Santanu Chakraborty

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  1. Jayeeta Samanta
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Correspondence to Arunima Sengupta.

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Samanta, J., Mondal, A., Saha, S. et al. Oleic Acid Protects from Arsenic-Induced Cardiac Hypertrophy via AMPK/FoxO/NFATc3 Pathway. Cardiovasc Toxicol 20, 261–280 (2020). https://doi.org/10.1007/s12012-019-09550-9

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