PMID- 33812930
OWN - NLM
STAT- MEDLINE
DCOM- 20211122
LR  - 20211122
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 753
DP  - 2021 May 14
TI  - Harpagide exerts a neuroprotective effect by inhibiting endoplasmic reticulum 
      stress via SERCA following oxygen-glucose deprivation/reoxygenation injury.
PG  - 135874
LID - S0304-3940(21)00252-4 [pii]
LID - 10.1016/j.neulet.2021.135874 [doi]
AB  - Cerebrovascular diseases endanger human health, and the physiological and 
      pathological processes of cerebral ischemia/reperfusion injury (CIRI) are 
      critical for the occurrence of these diseases and as targets for their treatment. 
      Here, we evaluated the effects of harpagide-mediated pharmacological and genetic 
      inhibition of sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) in vitro in PC12 
      cells. The molecular mechanism by which harpagide protects PC12 cells against 
      oxygen-glucose deprivation/reoxygenation (OGD/R) injury was investigated by 
      evaluating the cell survival rate with the 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, 
      assessing apoptosis by flow cytometry, determining the intracellular Ca(2+) 
      concentration ([Ca(2+)](i)) by laser scanning confocal microscopy (LSCM), and 
      measuring the expression of proteins related to SERCA and endoplasmic reticulum 
      stress (ERS) by Western blotting. The results revealed that harpagide 
      significantly decreased thapsigargin (TG)-induced apoptosis of PC12 cells, 
      downregulated the expression of ERS-related markers, considerably improved the 
      TG-induced expression of SERCA-related proteins and reduced the [Ca(2+)](i), 
      suggesting that harpagide effectively inhibited ERS directly. Moreover, harpagide 
      did not significantly reduce OGD/R-induced apoptosis but increased the expression 
      of ERS markers in PC12/SERCA(-) cells, indicating that harpagide targets SERCA to 
      protect against CIRI by suppressing ERS-mediated apoptosis.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Wang, Ke
AU  - Wang K
AD  - Medical College, Jiaxing University, Jiaxing, 314001, China. Electronic address: 
      kerrwong@163.com.
FAU - Wang, Tao
AU  - Wang T
AD  - China Coast Guard Hospital of the People's Armed Police Force, Jiaxing, 314001, 
      China.
FAU - Xu, Huang
AU  - Xu H
AD  - Medical College, Jiaxing University, Jiaxing, 314001, China.
FAU - Zhong, Xiaoming
AU  - Zhong X
AD  - College of Pharmacy, Zhe Jiang Chinese Medical University, Hangzhou, 310053, 
      China.
FAU - Huang, Zhen
AU  - Huang Z
AD  - College of Pharmacy, Zhe Jiang Chinese Medical University, Hangzhou, 310053, 
      China. Electronic address: huangzhen@zcmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210401
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Atp2a2 protein, rat)
RN  - 0 (Iridoid Glycosides)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Pyrans)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - IY9XDZ35W2 (Glucose)
RN  - OF59XHX7SR (harpagide)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Hypoxia/drug effects
MH  - Disease Models, Animal
MH  - Endoplasmic Reticulum/drug effects/pathology
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Gene Knockdown Techniques
MH  - Glucose/metabolism
MH  - Humans
MH  - Iridoid Glycosides/*pharmacology/therapeutic use
MH  - Ischemic Stroke/complications/*drug therapy/pathology
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Oxygen/metabolism
MH  - PC12 Cells
MH  - Pyrans/*pharmacology/therapeutic use
MH  - Rats
MH  - Reperfusion Injury/etiology/pathology/*prevention & control
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics/metabolism
OTO - NOTNLM
OT  - Cerebral ischemia reperfusion injury
OT  - Cytoplasmic calcium concentration
OT  - Harpagide
OT  - Lentivirus
OT  - SERCA
EDAT- 2021/04/05 06:00
MHDA- 2021/11/23 06:00
CRDT- 2021/04/04 20:40
PHST- 2021/01/18 00:00 [received]
PHST- 2021/03/24 00:00 [revised]
PHST- 2021/03/29 00:00 [accepted]
PHST- 2021/04/05 06:00 [pubmed]
PHST- 2021/11/23 06:00 [medline]
PHST- 2021/04/04 20:40 [entrez]
AID - S0304-3940(21)00252-4 [pii]
AID - 10.1016/j.neulet.2021.135874 [doi]
PST - ppublish
SO  - Neurosci Lett. 2021 May 14;753:135874. doi: 10.1016/j.neulet.2021.135874. Epub 
      2021 Apr 1.