Format

Send to

Choose Destination
J Biochem Mol Toxicol. 2017 Oct;31(10). doi: 10.1002/jbt.21942. Epub 2017 Jun 7.

Acute inhibitory effect of alpha-mangostin on sarcoplasmic reticulum calcium-ATPase and myocardial relaxation.

Author information

1
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
2
Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
3
Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
4
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, Thailand.

Abstract

The benefits of α-mangostin for various tissues have been reported, but its effect on the heart has not been clarified. This study aimed to evaluate the effects of α-mangostin on cardiac function. Using a cardiac sarcoplasmic reticulum (SR) membrane preparation, α-mangostin inhibited SR Ca2+ -ATPase activity in a dose-dependent manner (IC50 of 6.47 ± 0.7 μM). Its suppressive effect was specific to SR Ca2+ -ATPase but not to myofibrillar Ca2+ -ATPase. Using isolated cardiomyocytes, 50 μM of α-mangostin significantly increased the duration of cell relengthening and increased the duration of Ca2+ transient decay, suggesting altered myocyte relaxation. The relaxation effect of α-mangostin was also supported in vivo after intravenous infusion. A significant suppression of both peak pressure and rate of ventricular relaxation (-dP/dt) relative to DMSO infusion was observed. The results from the present study demonstrated that α-mangostin exerts specific inhibitory action on SR Ca2+ -ATPase activity, leading to myocardial relaxation dysfunction.

KEYWORDS:

SERCA; cardiomyocyte; intracellular Ca2+; myofilament

PMID:
28590578
DOI:
10.1002/jbt.21942
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center