PMID- 33973102
OWN - NLM
STAT- MEDLINE
DCOM- 20211018
LR  - 20211018
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 46
IP  - 8
DP  - 2021 Aug
TI  - TRESK Regulates Gm11874 to Induce Apoptosis of Spinal Cord Neurons via ATP5i 
      Mediated Oxidative Stress and DNA Damage.
PG  - 1970-1980
LID - 10.1007/s11064-021-03318-w [doi]
AB  - Reportedly, TWIK-related spinal cord K(+) (TRESK) deficiency in spinal cord 
      neurons positively correlates with the mechanism underlying neuropathic pain 
      (NP). However, the precise effects of TRESK on neurons of the spinal cord remain 
      elusive. In the present study, we investigated the impact of TRESK silencing on 
      spinal cord neurons to further elucidate the downstream mechanisms of TRESK. 
      Herein, neurons of the dorsal spinal cord were cultured as a cell model for 
      investigations. Apoptosis, oxidative stress, and DNA damage-related proteins were 
      evaluated. Additionally, flow cytometry, microarray profiling, real-time 
      polymerase chain reaction (PCR), western blotting, fluorescence in situ 
      hybridization (FISH), immunofluorescence, and enzyme-linked immunosorbent assay 
      (ELISA) were performed. In cultured neurons, the downregulation of TRESK mRNA 
      expression induced apoptosis of dorsal spinal cord neurons. Using real-time PCR 
      and western blotting, the upregulation of LncRNA Gm11874 (Gm11874) and ATP5i, 
      screened from the gene chip, was confirmed. On silencing TRESK, expression levels 
      of gamma-H2AX, poly [ADP-ribose] polymerase 1 (PARP-1), FoxO1, FoxO3, MitoSOX, 
      malondialdehyde (MDA), and 8-hydroxy-2' -deoxyguanosine (8-OHdG), which are known 
      indices of oxidative stress and DNA damage, were significantly elevated. 
      Moreover, ATP induced oxidative stress, DNA damage, and apoptosis were reduced by 
      ATP5i siRNA. Finally, Gm11874 and ATP5i were co-expressed in spinal cord neurons 
      in a FISH experiment, and the expression of ATP5i was positively regulated by 
      Gm11874. These results implied that ATP5i induced oxidative stress and DNA 
      damage, resulting in neuronal apoptosis, and Gm11874 was confirmed to act 
      upstream of ATP5i. Our study revealed that TRESK silencing upregulated Gm11874 to 
      induce apoptosis of spinal cord neurons, which resulted in ATP5i promoting 
      oxidative stress and DNA damage. These findings could highlight the 
      TRESK-mediated NP mechanism.
FAU - Liu, Pei
AU  - Liu P
AD  - Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical 
      University, Guangzhou, 510000, Guangdong Province, China.
FAU - Cheng, Ye
AU  - Cheng Y
AD  - Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical 
      University, Guangzhou, 510000, Guangdong Province, China.
FAU - Xu, Huiling
AU  - Xu H
AD  - Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical 
      University, Guangzhou, 510000, Guangdong Province, China.
FAU - Huang, Haicheng
AU  - Huang H
AD  - Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical 
      University, Guangzhou, 510000, Guangdong Province, China.
FAU - Tang, Simin
AU  - Tang S
AD  - Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical 
      University, Guangzhou, 510000, Guangdong Province, China.
FAU - Song, Fuhu
AU  - Song F
AD  - Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical 
      University, Guangzhou, 510000, Guangdong Province, China. songfuhu@126.com.
FAU - Zhou, Jun
AU  - Zhou J
AD  - Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical 
      University, Guangzhou, 510000, Guangdong Province, China. zhoujun7843@126.com.
LA  - eng
GR  - 81870879/National Natural Science Foundation of China/
GR  - 2017A030313534/Natural Science Foundation of Guangdong Province/
PT  - Journal Article
DEP - 20210510
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Potassium Channels)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Trik protein, mouse)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - DNA Damage/*physiology
MH  - Mice
MH  - Neurons/*metabolism
MH  - Oxidative Stress/*physiology
MH  - Potassium Channels/*metabolism
MH  - RNA, Long Noncoding/*metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Spinal Cord/cytology/metabolism
MH  - Up-Regulation/physiology
OTO - NOTNLM
OT  - ATP5i
OT  - Apoptosis
OT  - Gm11874
OT  - Oxidative stress
OT  - Spinal cord neurons
OT  - TRESK
EDAT- 2021/05/12 06:00
MHDA- 2021/10/21 06:00
CRDT- 2021/05/11 06:41
PHST- 2020/12/09 00:00 [received]
PHST- 2021/03/30 00:00 [accepted]
PHST- 2021/03/17 00:00 [revised]
PHST- 2021/05/12 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/05/11 06:41 [entrez]
AID - 10.1007/s11064-021-03318-w [pii]
AID - 10.1007/s11064-021-03318-w [doi]
PST - ppublish
SO  - Neurochem Res. 2021 Aug;46(8):1970-1980. doi: 10.1007/s11064-021-03318-w. Epub 
      2021 May 10.