NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores

被引：8

作者：

Gola, Lukas ^{[1
]}

Bierhansl, Laura ^{[1
]}

Csatari, Julia ^{[1
]}

Schroeter, Christina B. ^{[2
]}

Korn, Lisanne ^{[1
]}

Narayanan, Venu ^{[1
]}

Cerina, Manuela ^{[1
]}

Abdolahi, Sara ^{[3
]}

Speicher, Anna ^{[1
]}

Hermann, Alexander M. ^{[2
]}

Koenig, Simone ^{[4
]}

Dinkova-Kostova, Albena T. ^{[5
]}

Shekh-Ahmad, Tawfeeq ^{[6
]}

Meuth, Sven G. ^{[2
]}

Wiendl, Heinz ^{[1
]}

Gorji, Ali ^{[3
,7
]}

Pawlowski, Matthias ^{[1
]}

Kovac, Stjepana ^{[1
]}

机构：

[1] Univ Hosp Munster, Dept Neurol Inst Translat Neurol, D-48149 Munster, Germany

[2] Heinrich Heine Univ Dusseldorf, Med Fac, Dept Neurol, D-40225 Dusseldorf, Germany

[3] Khatam Alanbia Hosp, Shefa Neurosci Res Ctr, Tehran, Iran

[4] Univ Munster, Med Fac, Interdisciplinary Ctr Clin Res, Core Unit Prote, D-48149 Munster, Germany

[5] Univ Dundee, Sch Med, Div Cellular Med, Dundee DD1 9SY, Scotland

[6] Hebrew Univ Jerusalem, Inst Drug Res, Fac Med, Sch Pharm, IL-91120 Jerusalem, Israel

[7] Westfal Wilhelms Univ Munster, Epilepsy Res Ctr, D-48149 Munster, Germany

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2023年 / 80卷 / 05期

关键词：

Hyperexcitability; Reactive oxygen species (ROS); NADPH oxidase-4 (NOX4); Mitochondria; Calcium signaling; Neurodegeneration; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; BRAIN EXCITABILITY; NADPH OXIDASES; NOX ENZYMES; MITOCHONDRIA; ACTIVATION; REDOX; CUPRIZONE; SURVIVAL;

D O I：

10.1007/s00018-023-04758-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produce ROS and might have a regulating function during oxidative stress. We, therefore, aimed to determine the role of NOX4 on neuronal firing, hyperexcitability, and hyperexcitability-induced changes in neural network function. Using a multidimensional approach of an in vivo model of hyperexcitability, proteomic analysis, and cellular function analysis of ROS, mitochondrial integrity, and calcium levels, we demonstrate that NOX4 is neuroprotective by regulating ROS and calcium homeostasis and thereby preventing hyperexcitability and consequently neuronal death. These results implicate NOX4 as a potential redox regulator that is beneficial in hyperexcitability and thereby might have an important role in neurodegeneration.

引用

页数：18

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