Oxygen-Sensing Nox4 Generates Genotoxic ROS to Induce Premature Senescence of Nucleus Pulposus Cells through MAPK and NF-κB Pathways
Joint Authors
Liu, Huan
Zhou, Yue
Feng, Chencheng
Huang, Bo
Yang, Minghui
Lan, Minghong
Zhang, Yang
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-09-24
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Senescence is a crucial driver of intervertebral disc degeneration (IDD).
Disc cells are exposed to high oxygen tension due to neovascularization in degenerative discs.
However, the effect of oxygen tension on disc cell senescence was unknown.
Herein, rat nucleus pulposus (NP) cells were cultured under 20% O2 or 1% O2.
Consequently, ROS induced by 20% O2 caused DNA damage and then activated p53-p21-Rb and p16-Rb pathways via ERK signaling to induce NP cell senescence.
It also induced catabolic and proinflammatory phenotype of NP cells via MAPK and NF-κB pathways.
Furthermore, 20% O2 was found to upregulate Nox4 in NP cells.
Small interfering RNA against Nox4 reduced ROS production induced by 20% O2 and consequently suppressed premature senescence of NP cells.
On the contrary, NP cells overexpressing Nox4 produced more ROS and rapidly developed senescent signs.
In consistent with the in vitro studies, the expression of Nox4, p21, and Rb was upregulated in rat degenerative discs.
This study, for the first time, demonstrates that Nox4 is an oxygen-sensing enzyme and a main ROS source in NP cells.
Nox4-dependent ROS are genotoxic and a potent trigger of NP cell senescence.
Nox4 is a potential therapeutic target for disc cell senescence and IDD.
American Psychological Association (APA)
Feng, Chencheng& Zhang, Yang& Yang, Minghui& Lan, Minghong& Liu, Huan& Huang, Bo…[et al.]. 2017. Oxygen-Sensing Nox4 Generates Genotoxic ROS to Induce Premature Senescence of Nucleus Pulposus Cells through MAPK and NF-κB Pathways. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-15.
https://search.emarefa.net/detail/BIM-1195640
Modern Language Association (MLA)
Feng, Chencheng…[et al.]. Oxygen-Sensing Nox4 Generates Genotoxic ROS to Induce Premature Senescence of Nucleus Pulposus Cells through MAPK and NF-κB Pathways. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-15.
https://search.emarefa.net/detail/BIM-1195640
American Medical Association (AMA)
Feng, Chencheng& Zhang, Yang& Yang, Minghui& Lan, Minghong& Liu, Huan& Huang, Bo…[et al.]. Oxygen-Sensing Nox4 Generates Genotoxic ROS to Induce Premature Senescence of Nucleus Pulposus Cells through MAPK and NF-κB Pathways. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-15.
https://search.emarefa.net/detail/BIM-1195640
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1195640