Aquaporin-3 Attenuates Oxidative Stress-Induced Nucleus Pulposus Cell Apoptosis Through Regulating the P38 MAPK Pathway

• Published in: Cellular physiology and biochemistry Vol. 50; no. 5; pp. 1687 - 1697
• Main Authors: Xu, Yichun, Yao, Hui, Wang, Qiyou, Xu, Wenbin, Liu, Kaihua, Zhang, Junbin, Zhao, Huiqing, Hou, Gang
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Aquaporin 3 - genetics; Aquaporin 3 - metabolism; Aquaporin-3; Aquaporins; bcl-2-Associated X Protein - metabolism; Caspase 3 - metabolism; Cells, Cultured; Extracellular matrix; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Kinases; Nucleus pulposus; Nucleus Pulposus - cytology; Nucleus Pulposus - metabolism; Original Paper; Oxidative damage; Oxidative stress; Oxidative Stress - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism; Pathogenesis; Poly(ADP-ribose) Polymerases - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; United States > US; China; Aquaporin-3; Nucleus pulposus; Oxidative damage; Apoptosis
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000494788

Background/Aims: Previous studies have shown that oxidative damage is a main contributor to disc nucleus pulposus (NP) cell apoptosis. Aquaporin-3 (AQP-3) facilitates reactive oxygen species (ROS) scavenging and thus alleviates oxidative injury in other cells. This study aims to investigate the role and mechanism of AQP-3 in regulating NP cell apoptosis under oxidative damage. Methods: Rat NP cells were treated with H 2 O 2 for 48 hours, while control NP cells were free of H 2 O 2 . Recombinant AQP-3 lentiviral vectors were used to investigate the effect of enhanced AQP-3 expression levels in NP cells. NP cell apoptosis was assessed by flow cytometry, caspase-3 activity, gene expression of apoptosis-related molecules (Bax, Bcl-2 and caspase-3), and protein expression of cellular apoptosis markers (cleaved PARP and cleaved caspase-3). Additionally, intracellular ROS content and activity of the p38 MAPK pathway were evaluated. Results: Compared with the control NP cells, oxidative damage in the treatment cells significantly increased cell apoptosis ratios and caspase-3 activity, upregulated gene expression of Bax and caspase-3, downregulated gene expression of Bcl-2, and increased protein expression of cleaved PARP and cleaved caspase-3, as well as increased intracellular ROS content and activity of the p38 MAPK pathway. However, AQP-3 overexpression partly alleviated cell apoptosis, decreased intracellular ROS content, and inhibited the p38 MAPK pathway in NP cells under oxidative damage. Conclusion: Oxidative damage can significantly downregulate AQP-3 expression. Enhancing AQP-3 expression in NP cells partly attenuates cellular apoptosis through regulating the p38 MAPK pathway under oxidative damage.