4-Hydroxy-2-nonenal Induces Calcium Overload via the Generation of Reactive Oxygen Species in Isolated Rat Cardiac Myocytes

Kazufumi Nakamura, Daiji Miura, Kengo Fukushima Kusano, Yoshihisa Fujimoto, Wakako Sumita-Yoshikawa, Soichiro Fuke, Nobuhiro Nishii, Satoshi Nagase, Yoshiki Hata, Hiroshi Morita, Hiromi Matsubara, Tohru Ohe, Hiroshi Itoh

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background: It has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca2+ overload. Methods and Results: Exposure to HNE for 10 minutes in the presence of ferric nitrilotriacetate induced the production of hydroxyl radical (·OH) in the rat myocardium as assessed by electron spin resonance spectroscopy, and HNE induced the generation of reactive oxygen species (ROS) in a dose-dependent manner as assessed by 2′, 7′-dichlorofluorescein diacetate fluorescence. HNE increased intracellular Ca2+ concentration ([Ca2+]i) as assessed by fura-2 ratio in a dose- and time-dependent manner. After 20 minutes of HNE (400 μmol/L) exposure, hypercontracture was induced in 67% of the cells. Catalase, an antioxidative enzyme that can decompose hydrogen peroxide (H2O2), significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture. Carvedilol, a β-blocker with potent antioxidant activity, also significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture, but propranolol had no effect on either [Ca2+]i increase or hypercontracture. Conclusions: HNE induces the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. HNE formation may play an important role as a mediator of oxidative stress in heart failure.

Original languageEnglish
Pages (from-to)709-716
Number of pages8
JournalJournal of Cardiac Failure
Volume15
Issue number8
DOIs
Publication statusPublished - Oct 2009

Fingerprint

Cardiac Myocytes
Reactive Oxygen Species
Calcium
Myocardium
4-hydroxy-2-nonenal
2-nonenal
Fura-2
Electron Spin Resonance Spectroscopy
Aldehydes
Propranolol
Hydroxyl Radical
Catalase
Hydrogen Peroxide
Lipid Peroxidation
Oxidative Stress
Heart Failure
Antioxidants
Fluorescence
Enzymes

Keywords

  • calcium overload
  • heart failure
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

4-Hydroxy-2-nonenal Induces Calcium Overload via the Generation of Reactive Oxygen Species in Isolated Rat Cardiac Myocytes. / Nakamura, Kazufumi; Miura, Daiji; Kusano, Kengo Fukushima; Fujimoto, Yoshihisa; Sumita-Yoshikawa, Wakako; Fuke, Soichiro; Nishii, Nobuhiro; Nagase, Satoshi; Hata, Yoshiki; Morita, Hiroshi; Matsubara, Hiromi; Ohe, Tohru; Itoh, Hiroshi.

In: Journal of Cardiac Failure, Vol. 15, No. 8, 10.2009, p. 709-716.

Research output: Contribution to journalArticle

Nakamura, Kazufumi ; Miura, Daiji ; Kusano, Kengo Fukushima ; Fujimoto, Yoshihisa ; Sumita-Yoshikawa, Wakako ; Fuke, Soichiro ; Nishii, Nobuhiro ; Nagase, Satoshi ; Hata, Yoshiki ; Morita, Hiroshi ; Matsubara, Hiromi ; Ohe, Tohru ; Itoh, Hiroshi. / 4-Hydroxy-2-nonenal Induces Calcium Overload via the Generation of Reactive Oxygen Species in Isolated Rat Cardiac Myocytes. In: Journal of Cardiac Failure. 2009 ; Vol. 15, No. 8. pp. 709-716.
@article{601e06b366024313aefad6e903159a32,
title = "4-Hydroxy-2-nonenal Induces Calcium Overload via the Generation of Reactive Oxygen Species in Isolated Rat Cardiac Myocytes",
abstract = "Background: It has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca2+ overload. Methods and Results: Exposure to HNE for 10 minutes in the presence of ferric nitrilotriacetate induced the production of hydroxyl radical (·OH) in the rat myocardium as assessed by electron spin resonance spectroscopy, and HNE induced the generation of reactive oxygen species (ROS) in a dose-dependent manner as assessed by 2′, 7′-dichlorofluorescein diacetate fluorescence. HNE increased intracellular Ca2+ concentration ([Ca2+]i) as assessed by fura-2 ratio in a dose- and time-dependent manner. After 20 minutes of HNE (400 μmol/L) exposure, hypercontracture was induced in 67{\%} of the cells. Catalase, an antioxidative enzyme that can decompose hydrogen peroxide (H2O2), significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture. Carvedilol, a β-blocker with potent antioxidant activity, also significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture, but propranolol had no effect on either [Ca2+]i increase or hypercontracture. Conclusions: HNE induces the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. HNE formation may play an important role as a mediator of oxidative stress in heart failure.",
keywords = "calcium overload, heart failure, Reactive oxygen species",
author = "Kazufumi Nakamura and Daiji Miura and Kusano, {Kengo Fukushima} and Yoshihisa Fujimoto and Wakako Sumita-Yoshikawa and Soichiro Fuke and Nobuhiro Nishii and Satoshi Nagase and Yoshiki Hata and Hiroshi Morita and Hiromi Matsubara and Tohru Ohe and Hiroshi Itoh",
year = "2009",
month = "10",
doi = "10.1016/j.cardfail.2009.04.008",
language = "English",
volume = "15",
pages = "709--716",
journal = "Journal of Cardiac Failure",
issn = "1071-9164",
publisher = "Churchill Livingstone",
number = "8",

}

TY - JOUR

T1 - 4-Hydroxy-2-nonenal Induces Calcium Overload via the Generation of Reactive Oxygen Species in Isolated Rat Cardiac Myocytes

AU - Nakamura, Kazufumi

AU - Miura, Daiji

AU - Kusano, Kengo Fukushima

AU - Fujimoto, Yoshihisa

AU - Sumita-Yoshikawa, Wakako

AU - Fuke, Soichiro

AU - Nishii, Nobuhiro

AU - Nagase, Satoshi

AU - Hata, Yoshiki

AU - Morita, Hiroshi

AU - Matsubara, Hiromi

AU - Ohe, Tohru

AU - Itoh, Hiroshi

PY - 2009/10

Y1 - 2009/10

N2 - Background: It has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca2+ overload. Methods and Results: Exposure to HNE for 10 minutes in the presence of ferric nitrilotriacetate induced the production of hydroxyl radical (·OH) in the rat myocardium as assessed by electron spin resonance spectroscopy, and HNE induced the generation of reactive oxygen species (ROS) in a dose-dependent manner as assessed by 2′, 7′-dichlorofluorescein diacetate fluorescence. HNE increased intracellular Ca2+ concentration ([Ca2+]i) as assessed by fura-2 ratio in a dose- and time-dependent manner. After 20 minutes of HNE (400 μmol/L) exposure, hypercontracture was induced in 67% of the cells. Catalase, an antioxidative enzyme that can decompose hydrogen peroxide (H2O2), significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture. Carvedilol, a β-blocker with potent antioxidant activity, also significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture, but propranolol had no effect on either [Ca2+]i increase or hypercontracture. Conclusions: HNE induces the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. HNE formation may play an important role as a mediator of oxidative stress in heart failure.

AB - Background: It has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca2+ overload. Methods and Results: Exposure to HNE for 10 minutes in the presence of ferric nitrilotriacetate induced the production of hydroxyl radical (·OH) in the rat myocardium as assessed by electron spin resonance spectroscopy, and HNE induced the generation of reactive oxygen species (ROS) in a dose-dependent manner as assessed by 2′, 7′-dichlorofluorescein diacetate fluorescence. HNE increased intracellular Ca2+ concentration ([Ca2+]i) as assessed by fura-2 ratio in a dose- and time-dependent manner. After 20 minutes of HNE (400 μmol/L) exposure, hypercontracture was induced in 67% of the cells. Catalase, an antioxidative enzyme that can decompose hydrogen peroxide (H2O2), significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture. Carvedilol, a β-blocker with potent antioxidant activity, also significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture, but propranolol had no effect on either [Ca2+]i increase or hypercontracture. Conclusions: HNE induces the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. HNE formation may play an important role as a mediator of oxidative stress in heart failure.

KW - calcium overload

KW - heart failure

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=70349309267&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349309267&partnerID=8YFLogxK

U2 - 10.1016/j.cardfail.2009.04.008

DO - 10.1016/j.cardfail.2009.04.008

M3 - Article

C2 - 19786260

AN - SCOPUS:70349309267

VL - 15

SP - 709

EP - 716

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

SN - 1071-9164

IS - 8

ER -