Allopurinol modulates reactive oxygen species generation and Ca 2+ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes

Seok Min Kang; Soyeon Lim; Heesang Song; Woochul Chang; Sunju Lee; Sang Mee Bae; Ji Hyung Chung; Hakbae Lee; Ho Gyoung Kim; Deok Hyo Yoon; Tae Woong Kim; Yangsoo Jang; Jae Mo Sung; Nam Sik Chung; Ki Chul Hwang

doi:10.1016/j.ejphar.2006.01.013

Allopurinol modulates reactive oxygen species generation and Ca ²⁺ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes

Seok Min Kang, Soyeon Lim, Heesang Song, Woochul Chang, Sunju Lee, Sang Mee Bae, Ji Hyung Chung, Hakbae Lee, Ho Gyoung Kim, Deok Hyo Yoon, Tae Woong Kim, Yangsoo Jang, Jae Mo Sung, Nam Sik Chung, Ki Chul Hwang

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

40 Citations (Scopus)

Abstract

Myocardial oxidative stress and Ca²⁺ overload induced by ischemia-reperfusion may be involved in the development and progression of myocardial dysfunction in heart failure. Xanthine oxidase, which is capable of producing reactive oxygen species, is considered as a culprit regarding ischemia-reperfusion injury of cardiomyocytes. Even though inhibition of xanthine oxidase by allopurinol in failing hearts improves cardiac performance, the regulatory mechanisms are not known in detail. We therefore hypothesized that allopurinol may prevent the xanthine oxidase-induced reactive oxygen species production and Ca²⁺ overload, leading to decreased calcium-responsive signaling in myocardial dysfunction. Allopurinol reversed the increased xanthine oxidase activity in ischemia-reperfusion injury of neonatal rat hearts. Hypoxia-reoxygenation injury, which simulates ischemia-reperfusion injury, of neonatal rat cardiomyocytes resulted in activation of xanthine oxidase relative to that of the control, indicating that intracellular xanthine oxidase exists in neonatal rat cardiomyocytes and that hypoxia-reoxygenation induces xanthine oxidase activity. Allopurinol (10 μM) treatment suppressed xanthine oxidase activity induced by hypoxia-reoxygenation injury and the production of reactive oxygen species. Allopurinol also decreased the concentration of intracellular Ca²⁺ increased by enhanced xanthine oxidase activity. Enhanced xanthine oxidase activity resulted in decreased expression of protein kinase C and sarcoendoplasmic reticulum calcium ATPase and increased the phosphorylation of extracellular signal-regulated protein kinase and p38 kinase. Xanthine oxidase activity was increased in both ischemia-reperfusion-injured rat hearts and hypoxia-reoxygenation-injured cardiomyocytes, leading to reactive oxygen species production and intracellular Ca²⁺ overload through mechanisms involving p38 kinase and extracellular signal-regulated protein kinase (ERK) via sarcoendoplasmic reticulum calcium ATPase (SERCA) and protein kinase C (PKC). Xanthine oxidase inhibition with allopurinol modulates reactive oxygen species production and intracellular Ca²⁺ overload in hypoxia-reoxygenation-injured neonatal rat cardiomyocytes.

Original language	English
Pages (from-to)	212-219
Number of pages	8
Journal	European Journal of Pharmacology
Volume	535
Issue number	1-3
DOIs	https://doi.org/10.1016/j.ejphar.2006.01.013
Publication status	Published - 2006 Mar 27

Bibliographical note

Funding Information:
This work was supported by Yonsei University Research Fund of 2002 year and a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (HMP-00-GN-01-0001).

All Science Journal Classification (ASJC) codes

Pharmacology

Access to Document

10.1016/j.ejphar.2006.01.013

Cite this

Kang, S. M., Lim, S., Song, H., Chang, W., Lee, S., Bae, S. M., Chung, J. H., Lee, H., Kim, H. G., Yoon, D. H., Kim, T. W., Jang, Y., Sung, J. M., Chung, N. S., & Hwang, K. C. (2006). Allopurinol modulates reactive oxygen species generation and Ca ²⁺ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes. European Journal of Pharmacology, 535(1-3), 212-219. https://doi.org/10.1016/j.ejphar.2006.01.013

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title = "Allopurinol modulates reactive oxygen species generation and Ca 2+ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes",

abstract = "Myocardial oxidative stress and Ca2+ overload induced by ischemia-reperfusion may be involved in the development and progression of myocardial dysfunction in heart failure. Xanthine oxidase, which is capable of producing reactive oxygen species, is considered as a culprit regarding ischemia-reperfusion injury of cardiomyocytes. Even though inhibition of xanthine oxidase by allopurinol in failing hearts improves cardiac performance, the regulatory mechanisms are not known in detail. We therefore hypothesized that allopurinol may prevent the xanthine oxidase-induced reactive oxygen species production and Ca2+ overload, leading to decreased calcium-responsive signaling in myocardial dysfunction. Allopurinol reversed the increased xanthine oxidase activity in ischemia-reperfusion injury of neonatal rat hearts. Hypoxia-reoxygenation injury, which simulates ischemia-reperfusion injury, of neonatal rat cardiomyocytes resulted in activation of xanthine oxidase relative to that of the control, indicating that intracellular xanthine oxidase exists in neonatal rat cardiomyocytes and that hypoxia-reoxygenation induces xanthine oxidase activity. Allopurinol (10 μM) treatment suppressed xanthine oxidase activity induced by hypoxia-reoxygenation injury and the production of reactive oxygen species. Allopurinol also decreased the concentration of intracellular Ca2+ increased by enhanced xanthine oxidase activity. Enhanced xanthine oxidase activity resulted in decreased expression of protein kinase C and sarcoendoplasmic reticulum calcium ATPase and increased the phosphorylation of extracellular signal-regulated protein kinase and p38 kinase. Xanthine oxidase activity was increased in both ischemia-reperfusion-injured rat hearts and hypoxia-reoxygenation-injured cardiomyocytes, leading to reactive oxygen species production and intracellular Ca2+ overload through mechanisms involving p38 kinase and extracellular signal-regulated protein kinase (ERK) via sarcoendoplasmic reticulum calcium ATPase (SERCA) and protein kinase C (PKC). Xanthine oxidase inhibition with allopurinol modulates reactive oxygen species production and intracellular Ca2+ overload in hypoxia-reoxygenation-injured neonatal rat cardiomyocytes.",

author = "Kang, {Seok Min} and Soyeon Lim and Heesang Song and Woochul Chang and Sunju Lee and Bae, {Sang Mee} and Chung, {Ji Hyung} and Hakbae Lee and Kim, {Ho Gyoung} and Yoon, {Deok Hyo} and Kim, {Tae Woong} and Yangsoo Jang and Sung, {Jae Mo} and Chung, {Nam Sik} and Hwang, {Ki Chul}",

note = "Funding Information: This work was supported by Yonsei University Research Fund of 2002 year and a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (HMP-00-GN-01-0001).",

year = "2006",

month = mar,

day = "27",

doi = "10.1016/j.ejphar.2006.01.013",

language = "English",

volume = "535",

pages = "212--219",

journal = "European Journal of Pharmacology",

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publisher = "Elsevier",

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Kang, SM, Lim, S, Song, H, Chang, W, Lee, S, Bae, SM, Chung, JH, Lee, H, Kim, HG, Yoon, DH, Kim, TW, Jang, Y, Sung, JM, Chung, NS & Hwang, KC 2006, 'Allopurinol modulates reactive oxygen species generation and Ca ²⁺ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes', European Journal of Pharmacology, vol. 535, no. 1-3, pp. 212-219. https://doi.org/10.1016/j.ejphar.2006.01.013

TY - JOUR

T1 - Allopurinol modulates reactive oxygen species generation and Ca 2+ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes

AU - Kang, Seok Min

AU - Lim, Soyeon

AU - Song, Heesang

AU - Chang, Woochul

AU - Lee, Sunju

AU - Bae, Sang Mee

AU - Chung, Ji Hyung

AU - Lee, Hakbae

AU - Kim, Ho Gyoung

AU - Yoon, Deok Hyo

AU - Kim, Tae Woong

AU - Jang, Yangsoo

AU - Sung, Jae Mo

AU - Chung, Nam Sik

AU - Hwang, Ki Chul

N1 - Funding Information: This work was supported by Yonsei University Research Fund of 2002 year and a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (HMP-00-GN-01-0001).

PY - 2006/3/27

Y1 - 2006/3/27

N2 - Myocardial oxidative stress and Ca2+ overload induced by ischemia-reperfusion may be involved in the development and progression of myocardial dysfunction in heart failure. Xanthine oxidase, which is capable of producing reactive oxygen species, is considered as a culprit regarding ischemia-reperfusion injury of cardiomyocytes. Even though inhibition of xanthine oxidase by allopurinol in failing hearts improves cardiac performance, the regulatory mechanisms are not known in detail. We therefore hypothesized that allopurinol may prevent the xanthine oxidase-induced reactive oxygen species production and Ca2+ overload, leading to decreased calcium-responsive signaling in myocardial dysfunction. Allopurinol reversed the increased xanthine oxidase activity in ischemia-reperfusion injury of neonatal rat hearts. Hypoxia-reoxygenation injury, which simulates ischemia-reperfusion injury, of neonatal rat cardiomyocytes resulted in activation of xanthine oxidase relative to that of the control, indicating that intracellular xanthine oxidase exists in neonatal rat cardiomyocytes and that hypoxia-reoxygenation induces xanthine oxidase activity. Allopurinol (10 μM) treatment suppressed xanthine oxidase activity induced by hypoxia-reoxygenation injury and the production of reactive oxygen species. Allopurinol also decreased the concentration of intracellular Ca2+ increased by enhanced xanthine oxidase activity. Enhanced xanthine oxidase activity resulted in decreased expression of protein kinase C and sarcoendoplasmic reticulum calcium ATPase and increased the phosphorylation of extracellular signal-regulated protein kinase and p38 kinase. Xanthine oxidase activity was increased in both ischemia-reperfusion-injured rat hearts and hypoxia-reoxygenation-injured cardiomyocytes, leading to reactive oxygen species production and intracellular Ca2+ overload through mechanisms involving p38 kinase and extracellular signal-regulated protein kinase (ERK) via sarcoendoplasmic reticulum calcium ATPase (SERCA) and protein kinase C (PKC). Xanthine oxidase inhibition with allopurinol modulates reactive oxygen species production and intracellular Ca2+ overload in hypoxia-reoxygenation-injured neonatal rat cardiomyocytes.

AB - Myocardial oxidative stress and Ca2+ overload induced by ischemia-reperfusion may be involved in the development and progression of myocardial dysfunction in heart failure. Xanthine oxidase, which is capable of producing reactive oxygen species, is considered as a culprit regarding ischemia-reperfusion injury of cardiomyocytes. Even though inhibition of xanthine oxidase by allopurinol in failing hearts improves cardiac performance, the regulatory mechanisms are not known in detail. We therefore hypothesized that allopurinol may prevent the xanthine oxidase-induced reactive oxygen species production and Ca2+ overload, leading to decreased calcium-responsive signaling in myocardial dysfunction. Allopurinol reversed the increased xanthine oxidase activity in ischemia-reperfusion injury of neonatal rat hearts. Hypoxia-reoxygenation injury, which simulates ischemia-reperfusion injury, of neonatal rat cardiomyocytes resulted in activation of xanthine oxidase relative to that of the control, indicating that intracellular xanthine oxidase exists in neonatal rat cardiomyocytes and that hypoxia-reoxygenation induces xanthine oxidase activity. Allopurinol (10 μM) treatment suppressed xanthine oxidase activity induced by hypoxia-reoxygenation injury and the production of reactive oxygen species. Allopurinol also decreased the concentration of intracellular Ca2+ increased by enhanced xanthine oxidase activity. Enhanced xanthine oxidase activity resulted in decreased expression of protein kinase C and sarcoendoplasmic reticulum calcium ATPase and increased the phosphorylation of extracellular signal-regulated protein kinase and p38 kinase. Xanthine oxidase activity was increased in both ischemia-reperfusion-injured rat hearts and hypoxia-reoxygenation-injured cardiomyocytes, leading to reactive oxygen species production and intracellular Ca2+ overload through mechanisms involving p38 kinase and extracellular signal-regulated protein kinase (ERK) via sarcoendoplasmic reticulum calcium ATPase (SERCA) and protein kinase C (PKC). Xanthine oxidase inhibition with allopurinol modulates reactive oxygen species production and intracellular Ca2+ overload in hypoxia-reoxygenation-injured neonatal rat cardiomyocytes.

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