Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury

The mechanisms of cell injury resulting in a special type of cell death combining the features of apoptosis and necrosis were examined in Hep-2 cells exposed to 300 μM zinc sulfate during 24h. Acute exposure to zinc induced a rapid rise in metallothionein levels and increased oxidative stress occurr...

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Main Author: Emil Rudolf
Format: Article
Language:English
Published: Karolinum Press 2007-01-01
Series:Acta Medica
Subjects:
Online Access:https://actamedica.lfhk.cuni.cz/50/1/0043/
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author Emil Rudolf
author_facet Emil Rudolf
author_sort Emil Rudolf
collection DOAJ
description The mechanisms of cell injury resulting in a special type of cell death combining the features of apoptosis and necrosis were examined in Hep-2 cells exposed to 300 μM zinc sulfate during 24h. Acute exposure to zinc induced a rapid rise in metallothionein levels and increased oxidative stress occurring in the absence of a significant early ATP depletion. Accentuated ATP loss and elevated levels of superoxide at later treatment intervals (12h and longer) were present along with increased DNA damage. Manipulation with ATP production and inhibition of NADPH oxidase had a positive effect on zinc-related increase in oxidative stress and influenced the observed type of cell death. These results suggest that Hep-2 cells acutely exposed to zinc increase intracellular labile zinc stores and over express metalothioneins. Elevated production of peroxides in zinc-treated cells is at later treatment intervals accompanied by an increase in superoxide levels, possibly by activation of NADPH oxidase, DNA damage and severe ATP loss. Prevention of critical ATP depletion and, in particular, inhibition of oxidative stress attenuates zinc-mediated cell injury and stimulates apoptosis-like phenotype in exposed cells.
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spelling doaj.art-1a5331064a3244ec9574fe9893c4a5f22022-12-22T03:21:06ZengKarolinum PressActa Medica1211-42861805-96942007-01-01501434910.14712/18059694.2017.58Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell InjuryEmil Rudolf0Charles University in Prague, Faculty of Medicine in Hradec Králové, Department of Medical Biology and Genetics, Hradec Králové, Czech RepublicThe mechanisms of cell injury resulting in a special type of cell death combining the features of apoptosis and necrosis were examined in Hep-2 cells exposed to 300 μM zinc sulfate during 24h. Acute exposure to zinc induced a rapid rise in metallothionein levels and increased oxidative stress occurring in the absence of a significant early ATP depletion. Accentuated ATP loss and elevated levels of superoxide at later treatment intervals (12h and longer) were present along with increased DNA damage. Manipulation with ATP production and inhibition of NADPH oxidase had a positive effect on zinc-related increase in oxidative stress and influenced the observed type of cell death. These results suggest that Hep-2 cells acutely exposed to zinc increase intracellular labile zinc stores and over express metalothioneins. Elevated production of peroxides in zinc-treated cells is at later treatment intervals accompanied by an increase in superoxide levels, possibly by activation of NADPH oxidase, DNA damage and severe ATP loss. Prevention of critical ATP depletion and, in particular, inhibition of oxidative stress attenuates zinc-mediated cell injury and stimulates apoptosis-like phenotype in exposed cells.https://actamedica.lfhk.cuni.cz/50/1/0043/ZincApoptosisOxidative stressATPMetallothioneinNecrosis
spellingShingle Emil Rudolf
Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury
Acta Medica
Zinc
Apoptosis
Oxidative stress
ATP
Metallothionein
Necrosis
title Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury
title_full Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury
title_fullStr Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury
title_full_unstemmed Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury
title_short Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury
title_sort depletion of atp and oxidative stress underlie zinc induced cell injury
topic Zinc
Apoptosis
Oxidative stress
ATP
Metallothionein
Necrosis
url https://actamedica.lfhk.cuni.cz/50/1/0043/
work_keys_str_mv AT emilrudolf depletionofatpandoxidativestressunderliezincinducedcellinjury