Pathophysiology and Therapeutic Potential of NADPH Oxidases in Ischemic Stroke-Induced Oxidative Stress

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2021 Mar 29

PMID 33777315

Citations 30

Authors

Jinnan Duan

Shiqi Gao

Sheng Tu

Cameron Lenahan

Anwen Shao

Jifang Sheng

Affiliations

Soon will be listed here.

Abstract

Stroke is a leading cause of death and disability in humans. The excessive production of reactive oxygen species (ROS) is an important contributor to oxidative stress and secondary brain damage after stroke. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme complex consisting of membrane subunits and cytoplasmic subunits, regulates neuronal maturation and cerebrovascular homeostasis. However, NADPH oxidase overproduction contributes to neurotoxicity and cerebrovascular disease. NADPH oxidase has been implicated as the principal source of ROS in the brain, and numerous studies have shown that the knockout of NADPH exerts a protective effect in the model of ischemic stroke. In this review, we summarize the mechanism of activation of the NADPH oxidase family members, the pathophysiological effects of NADPH oxidase isoforms in ischemic stroke, and the studies of NADPH oxidase inhibitors to explore potential clinical applications.

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References

Jiang J, Chen X, Serizawa N, Szyndralewiez C, Page P, Schroder K . Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo. Free Radic Biol Med. 2012; 53(2):289-96. PMC: 3392471. DOI: 10.1016/j.freeradbiomed.2012.05.007. View

Altenhofer S, Radermacher K, Kleikers P, Wingler K, Schmidt H . Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement. Antioxid Redox Signal. 2014; 23(5):406-27. PMC: 4543484. DOI: 10.1089/ars.2013.5814. View

Kahles T, Luedike P, Endres M, Galla H, Steinmetz H, Busse R . NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke. Stroke. 2007; 38(11):3000-6. DOI: 10.1161/STROKEAHA.107.489765. View

Pluta R, Ulamek-Koziol M, Januszewski S, Czuczwar S . Amyloid pathology in the brain after ischemia. Folia Neuropathol. 2019; 57(3):220-226. DOI: 10.5114/fn.2019.88450. View

Abubaker A, Vara D, Visconte C, Eggleston I, Torti M, Canobbio I . Amyloid Peptide 1-42 Induces Integrin IIb3 Activation, Platelet Adhesion, and Thrombus Formation in a NADPH Oxidase-Dependent Manner. Oxid Med Cell Longev. 2019; 2019:1050476. PMC: 6441506. DOI: 10.1155/2019/1050476. View

Goulay R, Mena Romo L, Hol E, Dijkhuizen R . From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation. Transl Stroke Res. 2019; 11(4):601-614. PMC: 7340665. DOI: 10.1007/s12975-019-00755-2. View

Hecker L, Cheng J, Thannickal V . Targeting NOX enzymes in pulmonary fibrosis. Cell Mol Life Sci. 2012; 69(14):2365-71. PMC: 3710124. DOI: 10.1007/s00018-012-1012-7. View

Choi D, Kim J, Lee K, Kim H, Kim Y, Choi W . Role of neuronal NADPH oxidase 1 in the peri-infarct regions after stroke. PLoS One. 2015; 10(1):e0116814. PMC: 4305324. DOI: 10.1371/journal.pone.0116814. View

Prabhakaran S, Ruff I, Bernstein R . Acute stroke intervention: a systematic review. JAMA. 2015; 313(14):1451-62. DOI: 10.1001/jama.2015.3058. View

10.

Li T, Luo X, Wang E, Li N, Zhang X, Song F . Magnesium lithospermate B prevents phenotypic transformation of pulmonary arteries in rats with hypoxic pulmonary hypertension through suppression of NADPH oxidase. Eur J Pharmacol. 2019; 847:32-41. DOI: 10.1016/j.ejphar.2019.01.020. View

11.

Harvey A, Montezano A, Hood K, Lopes R, Rios F, Ceravolo G . Vascular dysfunction and fibrosis in stroke-prone spontaneously hypertensive rats: The aldosterone-mineralocorticoid receptor-Nox1 axis. Life Sci. 2017; 179:110-119. PMC: 5446265. DOI: 10.1016/j.lfs.2017.05.002. View

12.

Casas A, Kleikers P, Geuss E, Langhauser F, Adler T, Busch D . Calcium-dependent blood-brain barrier breakdown by NOX5 limits postreperfusion benefit in stroke. J Clin Invest. 2019; 129(4):1772-1778. PMC: 6436900. DOI: 10.1172/JCI124283. View

13.

Kalogeris T, Bao Y, Korthuis R . Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning. Redox Biol. 2014; 2:702-14. PMC: 4060303. DOI: 10.1016/j.redox.2014.05.006. View

14.

Thao-Vi Dao V, Elbatreek M, Altenhofer S, Casas A, Pachado M, Neullens C . Isoform-selective NADPH oxidase inhibitor panel for pharmacological target validation. Free Radic Biol Med. 2019; 148:60-69. DOI: 10.1016/j.freeradbiomed.2019.12.038. View

15.

Konior A, Schramm A, Czesnikiewicz-Guzik M, Guzik T . NADPH oxidases in vascular pathology. Antioxid Redox Signal. 2013; 20(17):2794-814. PMC: 4026218. DOI: 10.1089/ars.2013.5607. View

16.

Raz L, Zhang Q, Zhou C, Han D, Gulati P, Yang L . Role of Rac1 GTPase in NADPH oxidase activation and cognitive impairment following cerebral ischemia in the rat. PLoS One. 2010; 5(9):e12606. PMC: 2935374. DOI: 10.1371/journal.pone.0012606. View

17.

Ma M, Wang J, Zhang Q, Wang R, Dhandapani K, Vadlamudi R . NADPH oxidase in brain injury and neurodegenerative disorders. Mol Neurodegener. 2017; 12(1):7. PMC: 5240251. DOI: 10.1186/s13024-017-0150-7. View

18.

Lin D, Wang L, Yan S, Zhang Q, Zhang J, Shao A . The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression. Oxid Med Cell Longev. 2020; 2019:2491927. PMC: 7044480. DOI: 10.1155/2019/2491927. View

19.

Takac I, Schroder K, Zhang L, Lardy B, Anilkumar N, Lambeth J . The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4. J Biol Chem. 2011; 286(15):13304-13. PMC: 3075677. DOI: 10.1074/jbc.M110.192138. View

20.

Yang Q, Huang Q, Hu Z, Tang X . Potential Neuroprotective Treatment of Stroke: Targeting Excitotoxicity, Oxidative Stress, and Inflammation. Front Neurosci. 2019; 13:1036. PMC: 6777147. DOI: 10.3389/fnins.2019.01036. View