PMID- 31263165
OWN - NLM
STAT- MEDLINE
DCOM- 20200713
LR  - 20210110
IS  - 2041-4889 (Electronic)
VI  - 10
IP  - 7
DP  - 2019 Jul 1
TI  - Nrf2 drives oxidative stress-induced autophagy in nucleus pulposus cells via a 
      Keap1/Nrf2/p62 feedback loop to protect intervertebral disc from degeneration.
PG  - 510
LID - 10.1038/s41419-019-1701-3 [doi]
LID - 510
AB  - Intervertebral disc (IVD) degeneration is known to aggravate with age and 
      oxidative stress is implicated in the pathogenesis of many age-related diseases. 
      Nuclear factor (erythroid-derived-2)-like 2 (Nrf2) can confer adaptive protection 
      against oxidative and proteotoxic stress in cells. In this study, we assessed 
      whether Nrf2 can protect against oxidative stress in nucleus pulposus (NP) cells. 
      In addition, we investigated Nrf2 expression in NP tissue samples from patients 
      with different degrees of IVD degeneration and a mouse model of aging and IVD 
      degeneration and the influence of H(2)O(2)-induced oxidative stress on autophagic 
      pathways in NP cells. Autophagy was assessed by measuring levels of 
      autophagy-related protein (ATG) family members and the autophagic markers, p62 
      and LC3. We found that expression of Nrf2 progressively decreased in human NP 
      tissue samples of patients with increasing degrees of IVD degeneration. Nrf2 
      deficiency leads to the degeneration of IVDs during aging. Nrf2 knockout also 
      aggravates IVD degeneration and reduces autophagic gene expression in an induced 
      mouse model of IVD degeneration. The detrimental effects of H(2)O(2)-induced 
      oxidative stress were increased in autophagy-deficient cells via reduced 
      expression of Atg7 and the Keap1-Nrf2-p62 autophagy pathway. Taken together, 
      these results suggest that excessive oxidative stress causes the upregulation of 
      autophagy, and autophagy acts as an antioxidant feedback response activated by a 
      Keap1-Nrf2-p62 feedback loop in IVD degeneration.
FAU - Tang, Zehan
AU  - Tang Z
AD  - Department of Spinal Surgery, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Hu, Bo
AU  - Hu B
AD  - Department of Spinal Surgery, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Zang, Fazhi
AU  - Zang F
AD  - Department of Spinal Surgery, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Wang, Jianxi
AU  - Wang J
AD  - Department of Spinal Surgery, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Zhang, Xingda
AU  - Zhang X
AD  - Department of Spinal Surgery, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Chen, Huajiang
AU  - Chen H
AD  - Department of Spinal Surgery, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China. spine.chen@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190701
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (KEAP1 protein, human)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Autophagy/genetics/physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - Intervertebral Disc/*metabolism/pathology
MH  - Intervertebral Disc Degeneration/*metabolism/pathology
MH  - Kelch-Like ECH-Associated Protein 1/genetics/*metabolism
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Nucleus Pulposus/*metabolism
MH  - Oxidation-Reduction
MH  - Oxidative Stress/genetics/physiology
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction/genetics/physiology
MH  - Young Adult
PMC - PMC6602960
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/07/03 06:00
MHDA- 2020/07/14 06:00
PMCR- 2019/07/01
CRDT- 2019/07/03 06:00
PHST- 2018/10/26 00:00 [received]
PHST- 2019/05/29 00:00 [accepted]
PHST- 2019/05/28 00:00 [revised]
PHST- 2019/07/03 06:00 [entrez]
PHST- 2019/07/03 06:00 [pubmed]
PHST- 2020/07/14 06:00 [medline]
PHST- 2019/07/01 00:00 [pmc-release]
AID - 10.1038/s41419-019-1701-3 [pii]
AID - 1701 [pii]
AID - 10.1038/s41419-019-1701-3 [doi]
PST - epublish
SO  - Cell Death Dis. 2019 Jul 1;10(7):510. doi: 10.1038/s41419-019-1701-3.