bims-noxint 2022-04-17 papers

Issue of 2022–04–17
three papers selected by
Laia Caja Puigsubira, Uppsala University

Mol Cell Endocrinol. 2022 Apr 09. pii: S0303-7207(22)00093-4. [Epub ahead of print] 111645

Inhibition of Nicotinamide adenine dinucleotide phosphate oxidase 4 attenuates cell apoptosis and oxidative stress in a rat model of polycystic ovary syndrome through the activation of Nrf-2/HO-1 signaling pathway.

Yan Li, Jia Xu, Lingxia Li, Lu Bai, Yunping Wang, Jianfang Zhang, Haixu Wang.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-aged women. In this study, a rat model of PCOS was established by subcutaneous injection of dehydroepiandrosterone (DHEA). NOX4 was highly expressed in PCOS rat ovaries, while its specific role in PCOS remains unclear. Lentivirus-mediated shRNA targeting NOX4 inhibited oxidative stress by reducing ROS, 4-HNE and MDA levels, and increasing SOD and GPX activities in rat ovaries. NOX4 deficiency increased Bcl-2 levels and decreased Bax, cleaved caspase-3 and cleaved caspase-9 levels and DHEA-induced cell apoptosis in rat ovaries. Similar to the in vivo results, NOX4 silencing inhibited oxidative stress and cell apoptosis in DHEA-treated rat granulosa cells. Moreover, NOX4 silencing promoted Nrf-2 translocation, and the expression of Nrf-2 and HO-1 both in vivo and in vitro. Thus, NOX4 deficiency may ameliorate PCOS in rats by reducing oxidative stress and cell apoptosis via activating the Nrf-2/HO-1 signal pathway.

Keywords: Apoptosis; Granulosa cells; NOX4; Nrf-2; Oxidative stress; PCOS

DOI: https://doi.org/10.1016/j.mce.2022.111645

Oxid Med Cell Longev. 2022 ;2022 3494262

miR-92b-3p Exerts Neuroprotective Effects on Ischemia/Reperfusion-Induced Cerebral Injury via Targeting NOX4 in a Rat Model.

Yongpan Huang, Jiayu Tang, Xiaojuan Li, Xian Long, Yansong Huang, Xi Zhang.

The necessity to increase the efficiency of organ preservation has pushed researchers to consider the mechanisms to minimize cerebral ischemia/reperfusion (I/R) injury. Hence, we evaluated the role of the miR-92b-3p/NOX4 pathway in cerebral I/R injury. A cerebral I/R injury model was established by blocking the left middle cerebral artery for 2 h and reperfusion for 24 h, and a hypoxia/reoxygenation (H/R) model was established. Thereafter, cerebral I/R increased obvious neurobiological function and brain injury (such as cerebral infarction, apoptosis, and cell morphology changes). In addition, we noted a significant decrease in the expression of miR-92b-3p, as well as increases in apoptosis and oxidative stress and an increase in NOX4. Furthermore, overexpression of miR-92b-3p blocked the inhibitory effect of miR-92b-3p on the expression of NOX4 and the accumulation of oxygen-free radicals. Bioinformatics analysis found that NOX4 may be the target gene regulated by miR-92b-3p. In conclusion, the involvement of the miR-92b-3p/NOX4 pathway ameliorated cerebral I/R injury through the prevention of apoptosis and oxidative stress. The miR-92b-3p/NOX4 pathway could be considered a potential therapeutic target to alleviate cerebral I/R injury.

DOI: https://doi.org/10.1155/2022/3494262

Cell Death Dis. 2022 Apr 13. 13(4): 341

Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production.

Qipeng Wu, Le Li, Chunmeng Miao, Muhammad Hasnat, Lixin Sun, Zhenzhou Jiang, Luyong Zhang.

Osteopontin (OPN) is a multifunctional cytokine that can impact cancer progression. Therefore, it is crucial to determine the key factors involved in the biological role of OPN for the development of treatment. Here, we investigated that OPN promoted hepatocellular carcinoma (HCC) cell proliferation and migration by increasing Reactive oxygen species (ROS) production and disclosed the underlying mechanism. Knockdown of OPN suppressed ROS production in vitro and in vivo, whereas treatment with human recombinant OPN produced the opposite effect. N-Acetyl-L-cysteine (NAC, ROS scavenger) partially blocked HCC cell proliferation and migration induced by OPN. Mechanistically, OPN induced ROS production in HCC cells by upregulating the expression of NADPH oxidase 1 (NOX1). NOX1 knockdown in HCC cells partially abrogated the cell proliferation and migration induced by OPN. Moreover, inhibition of JAK2/STAT3 phosphorylation effectively decreased the transcription of NOX1, upregulated by OPN. In addition, NOX1 overexpression increased JAK2 and STAT3 phosphorylation by increasing ROS production, creating a positive feedback loop for stimulating JAK2/STAT3 signaling induced by OPN. This study for the first time demonstrated that HCC cells utilized OPN to generate ROS for tumor progression, and disruption of OPN/NOX1 axis might be a promising therapeutic strategy for HCC.

DOI: https://doi.org/10.1038/s41419-022-04806-9