Role of glutathione in protecting endothelial cells against hydrogen peroxide oxidant injury

Sharon Andreoli, Colleen P. Mallett, Jerry M. Bergstein

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

To determine the mechanism responsible for the enhanced susceptibility of endothelial cells to oxidant injury in the absence of glucose, we induced endothelial cell injury with oxygen radicals in the presence of various oxygen radical scavengers and measured endothelial cell levels of glutathione after oxidant injury in the presence and absence of glucose. Endothelial cells were damaged with toxic oxygen radicals generated by phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs) or xanthine-xanthine oxidase in the presence and absence of glucose and catalase (scavenger of hydrogen peroxide), superoxide dismutase (scavenger of superoxide radical), isoleucine, valine, and serine (scavengers of hypochlorous acid), or mannitol, ethanol, benzoic acid, dimethyl sulfoxide, and dimethyl thiourea (scavengers of hydroxyl radical). Endothelial cell injury was quantitated by 2-deoxy-[1-3H] glucose or chromium 51 release assays or both. In each oxidant-generating system, in the presence and absence of glucose, only catalase significantly protected endothelial cells from oxidant injury (P < 0.001). When endothelial cells were damaged by hydrogen peroxide generated with xanthine-xanthine oxidase in the presence of glucose, endothelial cell levels of glutathione remained unchanged. In contrast, when endothelial cells were damaged with xanthine-xanthine oxidase in the absence of glucose, endothelial cell levels of glutathione fell to <50% of baseline (P < 0.05). Xanthine-xanthine oxidase-mediated endothelial cell damage and depletion of glutathione in the absence of glucose were similar to results obtained in the presence of glucose when glutathione was depleted with buthionine sulfoximine, diethyl maleate, or 1-chloro-2,4-dinitrobenzene. We conclude that hydrogen peroxide is the oxygen species responsible for endothelial cell damage from PMA-activated PMNs and xanthine-xanthine oxidase in the presence and absence of glucose and that enhanced endothelial cell susceptibility to hydrogen peroxide-mediated oxidant injury in the absence of glucose is a result of depletion of glutathione stores, which are important in detoxifying hydrogen peroxide.

Original languageEnglish
Pages (from-to)182-189
Number of pages8
JournalJournal of Laboratory and Clinical Medicine
Volume108
Issue number3
StatePublished - 1986

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Endothelial cells
Oxidants
Hydrogen Peroxide
Glutathione
Endothelial Cells
Wounds and Injuries
Glucose
Xanthine
Xanthine Oxidase
Reactive Oxygen Species
diethyl maleate
Tetradecanoylphorbol Acetate
Catalase
Buthionine Sulfoximine
Hypochlorous Acid
Dinitrochlorobenzene
Thiourea
Benzoic Acid
Isoleucine
Poisons

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Role of glutathione in protecting endothelial cells against hydrogen peroxide oxidant injury. / Andreoli, Sharon; Mallett, Colleen P.; Bergstein, Jerry M.

In: Journal of Laboratory and Clinical Medicine, Vol. 108, No. 3, 1986, p. 182-189.

Research output: Contribution to journalArticle

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abstract = "To determine the mechanism responsible for the enhanced susceptibility of endothelial cells to oxidant injury in the absence of glucose, we induced endothelial cell injury with oxygen radicals in the presence of various oxygen radical scavengers and measured endothelial cell levels of glutathione after oxidant injury in the presence and absence of glucose. Endothelial cells were damaged with toxic oxygen radicals generated by phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs) or xanthine-xanthine oxidase in the presence and absence of glucose and catalase (scavenger of hydrogen peroxide), superoxide dismutase (scavenger of superoxide radical), isoleucine, valine, and serine (scavengers of hypochlorous acid), or mannitol, ethanol, benzoic acid, dimethyl sulfoxide, and dimethyl thiourea (scavengers of hydroxyl radical). Endothelial cell injury was quantitated by 2-deoxy-[1-3H] glucose or chromium 51 release assays or both. In each oxidant-generating system, in the presence and absence of glucose, only catalase significantly protected endothelial cells from oxidant injury (P < 0.001). When endothelial cells were damaged by hydrogen peroxide generated with xanthine-xanthine oxidase in the presence of glucose, endothelial cell levels of glutathione remained unchanged. In contrast, when endothelial cells were damaged with xanthine-xanthine oxidase in the absence of glucose, endothelial cell levels of glutathione fell to <50{\%} of baseline (P < 0.05). Xanthine-xanthine oxidase-mediated endothelial cell damage and depletion of glutathione in the absence of glucose were similar to results obtained in the presence of glucose when glutathione was depleted with buthionine sulfoximine, diethyl maleate, or 1-chloro-2,4-dinitrobenzene. We conclude that hydrogen peroxide is the oxygen species responsible for endothelial cell damage from PMA-activated PMNs and xanthine-xanthine oxidase in the presence and absence of glucose and that enhanced endothelial cell susceptibility to hydrogen peroxide-mediated oxidant injury in the absence of glucose is a result of depletion of glutathione stores, which are important in detoxifying hydrogen peroxide.",
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N2 - To determine the mechanism responsible for the enhanced susceptibility of endothelial cells to oxidant injury in the absence of glucose, we induced endothelial cell injury with oxygen radicals in the presence of various oxygen radical scavengers and measured endothelial cell levels of glutathione after oxidant injury in the presence and absence of glucose. Endothelial cells were damaged with toxic oxygen radicals generated by phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs) or xanthine-xanthine oxidase in the presence and absence of glucose and catalase (scavenger of hydrogen peroxide), superoxide dismutase (scavenger of superoxide radical), isoleucine, valine, and serine (scavengers of hypochlorous acid), or mannitol, ethanol, benzoic acid, dimethyl sulfoxide, and dimethyl thiourea (scavengers of hydroxyl radical). Endothelial cell injury was quantitated by 2-deoxy-[1-3H] glucose or chromium 51 release assays or both. In each oxidant-generating system, in the presence and absence of glucose, only catalase significantly protected endothelial cells from oxidant injury (P < 0.001). When endothelial cells were damaged by hydrogen peroxide generated with xanthine-xanthine oxidase in the presence of glucose, endothelial cell levels of glutathione remained unchanged. In contrast, when endothelial cells were damaged with xanthine-xanthine oxidase in the absence of glucose, endothelial cell levels of glutathione fell to <50% of baseline (P < 0.05). Xanthine-xanthine oxidase-mediated endothelial cell damage and depletion of glutathione in the absence of glucose were similar to results obtained in the presence of glucose when glutathione was depleted with buthionine sulfoximine, diethyl maleate, or 1-chloro-2,4-dinitrobenzene. We conclude that hydrogen peroxide is the oxygen species responsible for endothelial cell damage from PMA-activated PMNs and xanthine-xanthine oxidase in the presence and absence of glucose and that enhanced endothelial cell susceptibility to hydrogen peroxide-mediated oxidant injury in the absence of glucose is a result of depletion of glutathione stores, which are important in detoxifying hydrogen peroxide.

AB - To determine the mechanism responsible for the enhanced susceptibility of endothelial cells to oxidant injury in the absence of glucose, we induced endothelial cell injury with oxygen radicals in the presence of various oxygen radical scavengers and measured endothelial cell levels of glutathione after oxidant injury in the presence and absence of glucose. Endothelial cells were damaged with toxic oxygen radicals generated by phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs) or xanthine-xanthine oxidase in the presence and absence of glucose and catalase (scavenger of hydrogen peroxide), superoxide dismutase (scavenger of superoxide radical), isoleucine, valine, and serine (scavengers of hypochlorous acid), or mannitol, ethanol, benzoic acid, dimethyl sulfoxide, and dimethyl thiourea (scavengers of hydroxyl radical). Endothelial cell injury was quantitated by 2-deoxy-[1-3H] glucose or chromium 51 release assays or both. In each oxidant-generating system, in the presence and absence of glucose, only catalase significantly protected endothelial cells from oxidant injury (P < 0.001). When endothelial cells were damaged by hydrogen peroxide generated with xanthine-xanthine oxidase in the presence of glucose, endothelial cell levels of glutathione remained unchanged. In contrast, when endothelial cells were damaged with xanthine-xanthine oxidase in the absence of glucose, endothelial cell levels of glutathione fell to <50% of baseline (P < 0.05). Xanthine-xanthine oxidase-mediated endothelial cell damage and depletion of glutathione in the absence of glucose were similar to results obtained in the presence of glucose when glutathione was depleted with buthionine sulfoximine, diethyl maleate, or 1-chloro-2,4-dinitrobenzene. We conclude that hydrogen peroxide is the oxygen species responsible for endothelial cell damage from PMA-activated PMNs and xanthine-xanthine oxidase in the presence and absence of glucose and that enhanced endothelial cell susceptibility to hydrogen peroxide-mediated oxidant injury in the absence of glucose is a result of depletion of glutathione stores, which are important in detoxifying hydrogen peroxide.

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