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bioRxiv · 10.1101/2021.11.21.469451

Nrf2 mediated ER-phagy protects against oxidative damage in intervertebral disc degeneration

lin, z.·ni, l.·teng, c.·zhang, z.·lu, x.·xie, c.·wu, l.·zhou, y.·tian, n.·wu, y.·sun, l.·pan, z.·wang, x.·Zhang, X.
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Abstract

Intervertebral disc degeneration (IDD) increases the risk of low back pain (LBP). Oxidative stress may induce cellular damage and contribute to various diseases including IDD. Endoplasmic reticulum autophagy (ER-phagy) is a specific type of autophagy, its role in oxidative stress induced damage as well as in IDD is unknown. This study explores the role of ER-phagy in oxidative damage in intervertebral disc nucleus pulposus cells (NPCs), as well as the Nrf2/FAM134B axis in ER-phagy regulation and IDD therapy. We found ER-phagy was decreased in NPCs during oxidative stress; while FAM134B may promote ER-phagy and alleviate oxidative stress induced ER-stress and apoptosis. In addition, the nuclear transcription factor Nrf2 may promote the expression of FAM134B as well as ER-phagy, and suppress ER-stress and apoptosis in NPCs. Furthermore, overexpression of FAM134B and Nrf2 could effectively attenuate the progression of IDD in rats in vivo. These results suggest Nrf2/FAM134B mediated ER-phagy may combat oxidative damage in cells; meanwhile, ER-phagy as well as Nrf2 could be potential therapeutic targets for IDD. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/469451v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@188b390org.highwire.dtl.DTLVardef@1c4e4f6org.highwire.dtl.DTLVardef@193fe77org.highwire.dtl.DTLVardef@12770e2_HPS_FORMAT_FIGEXP M_FIG C_FIG

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lin, z., ni, l., teng, c., zhang, z., lu, x., xie, c., wu, l., zhou, y., tian, n., wu, y., sun, l., pan, z., wang, x., Zhang, X.. 2021-11-22. Nrf2 mediated ER-phagy protects against oxidative damage in intervertebral disc degeneration. https://doi.org/10.1101/2021.11.21.469451

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