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

Sukanya Phungphong; Anusak Kijtawornrat; Pieter P. de Tombe; Jonggonnee Wattanapermpool; Tepmanas Bupha-Intr; Sunit Suksamrarn

doi:10.1002/jbt.21942

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

Sukanya Phungphong
, Anusak Kijtawornrat
, Pieter P. de Tombe
, Jonggonnee Wattanapermpool
, Tepmanas Bupha-Intr
, Sunit Suksamrarn

Mahidol University
Chulalongkorn University
Stritch School of Medicine
Srinakharinwirot University

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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.

Original language	English
Article number	e21942
Journal	Journal of Biochemical and Molecular Toxicology
Volume	31
Issue number	10
DOIs	https://doi.org/10.1002/jbt.21942
Publication status	Published - Oct 2017
Externally published	Yes

Keywords

SERCA
cardiomyocyte
intracellular Ca
myofilament

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10.1002/jbt.21942

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@article{a088ceaa366f43b1bb0516f1da518ff3,

title = "Acute inhibitory effect of alpha-mangostin on sarcoplasmic reticulum calcium-ATPase and myocardial relaxation",

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 ({\textendash}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 Ca, myofilament",

author = "Sukanya Phungphong and Anusak Kijtawornrat and \{de Tombe\}, \{Pieter P.\} and Jonggonnee Wattanapermpool and Tepmanas Bupha-Intr and Sunit Suksamrarn",

note = "Publisher Copyright: {\textcopyright} 2017 Wiley Periodicals, Inc.",

year = "2017",

month = oct,

doi = "10.1002/jbt.21942",

language = "English",

volume = "31",

journal = "Journal of Biochemical and Molecular Toxicology",

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T1 - Acute inhibitory effect of alpha-mangostin on sarcoplasmic reticulum calcium-ATPase and myocardial relaxation

AU - Phungphong, Sukanya

AU - Kijtawornrat, Anusak

AU - de Tombe, Pieter P.

AU - Wattanapermpool, Jonggonnee

AU - Bupha-Intr, Tepmanas

AU - Suksamrarn, Sunit

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - SERCA

KW - cardiomyocyte

KW - intracellular Ca

KW - myofilament

UR - https://www.scopus.com/pages/publications/85020256751

U2 - 10.1002/jbt.21942

DO - 10.1002/jbt.21942

M3 - Article

C2 - 28590578

AN - SCOPUS:85020256751

SN - 1095-6670

VL - 31

JO - Journal of Biochemical and Molecular Toxicology

JF - Journal of Biochemical and Molecular Toxicology

IS - 10

M1 - e21942

ER -

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

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Keywords

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