Leu27 IGF-II-induced hypertrophy in H9c2 cardiomyoblasts is ameliorated by saffron by regulation of calcineurin/NFAT and CaMKIIδ signaling

Chin-Yi Lin; Marthandam Asokan Shibu; Renee Wen; Cecilia Hsuan Day; Ray-Jade Chen; Chia-Hua Kuo; Tsung-Jung Ho; Vijaya Padma Viswanadha; Wei-Wen Kuo; Chih-Yang Huang

doi:10.1002/tox.23360

Leu²⁷ IGF-II-induced hypertrophy in H9c2 cardiomyoblasts is ameliorated by saffron by regulation of calcineurin/NFAT and CaMKIIδ signaling

Environ Toxicol. 2021 Dec;36(12):2475-2483. doi: 10.1002/tox.23360. Epub 2021 Sep 8.

Authors

Chin-Yi Lin^{1

2}, Marthandam Asokan Shibu³, Renee Wen^{4

5

6}, Cecilia Hsuan Day⁷, Ray-Jade Chen⁸, Chia-Hua Kuo⁹, Tsung-Jung Ho^{10

11

12}, Vijaya Padma Viswanadha¹³, Wei-Wen Kuo^{14

15}, Chih-Yang Huang^{3

16

17

18

19}

Affiliations

¹ Ph.D. Program for Aging, China Medical University, Taichung, Taiwan.
² Department of Chinese Medicine, Yuan Sheng Hospital, ChangHua, Taiwan.
³ Cardiovascular and Mitochondria Related Diseases Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
⁴ Walnut High School, Walnut, California, USA.
⁵ Department of Dermatology, Taipei City Hospital, Taipei, Taiwan.
⁶ Department of Biological Science and Technology, College of Biopharmaceutical and Food Science, China Medical University, Taichung, Taiwan.
⁷ Department of Nursing, Mei Ho University, Pingtung, Taiwan.
⁸ Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁹ Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.
¹⁰ Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
¹¹ Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
¹² School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan.
¹³ Department of Biotechnology, Bharathiar University, Coimbatore, India.
¹⁴ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
¹⁵ Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, Taiwan.
¹⁶ Graduate Institute of Biomedical sciences, China Medical University, Taichung, Taiwan.
¹⁷ Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
¹⁸ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
¹⁹ Department of Biotechnology, Asia University, Taichung, Taiwan.

PMID: 34495567
DOI: 10.1002/tox.23360

Abstract

The insulin-like growth factor II receptor (IGF-IIR) induces myocardial hypertrophy under various pathological conditions like diabetes and hypertension via G protein receptors like Gαq or Gαs. Increased expression of the ligand IGF II and IGF-IIR induces pathological hypertrophy through downstream signaling mediators such as calcineurin, nuclear factor of activated T cells 3 and calcium-calmodulin (CaM)-dependent kinase II (CaMKII)-histone deacetylase 4 (HDAC4). The dried stigma of Crocus sativus L. (saffron) has a long repute as a traditional medicine against various disorders. In the present study, we have investigated whether C. sativus extract (CSE) canameliorate Leu²⁷ IGF-II triggered hypertrophy and have elucidated the underlying mechanism of protection. Additionally, the effects of oleic acid (OA), an activator of calcineurin and CaMKII was investigated thereof. The results demonstrate that CSE can ameliorate Leu²⁷ IGF-II-induced hypertrophy seemingly through regulation of calcineurin-NFAT3 and CaMKII-HDAC4 signaling cascade.

Keywords: CaMKII; NFATc3; calcineurin; cardiac hypertrophy; saffron.

MeSH terms

Calcineurin*
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
Crocus*
Hypertrophy
Insulin-Like Growth Factor II / genetics
Myocytes, Cardiac

Substances

Insulin-Like Growth Factor II
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcineurin

Abstract

MeSH terms

Substances

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