PMID- 31167655
OWN - NLM
STAT- MEDLINE
DCOM- 20191202
LR  - 20200225
IS  - 1423-0127 (Electronic)
IS  - 1021-7770 (Print)
IS  - 1021-7770 (Linking)
VI  - 26
IP  - 1
DP  - 2019 Jun 5
TI  - Pinin protects astrocytes from cell death after acute ischemic stroke via 
      maintenance of mitochondrial anti-apoptotic and bioenergetics functions.
PG  - 43
LID - 10.1186/s12929-019-0538-5 [doi]
LID - 43
AB  - BACKGROUND: Stroke is the second most common cause of deaths worldwide. After an 
      ischemic stroke, the proliferated reactive astrocytes in the peri-infarct areas 
      play a beneficial role in neuronal survival. As such, astrocytes have gradually 
      become a target for neuroprotection in stroke. The present study assessed the 
      hypothesis that Pinin (Pnn), originally identified as a nuclear and 
      desmosome-associated protein and is now known to possess anti-apoptotic capacity, 
      protects astrocytes from cell death after ischemic stroke and delineated the 
      underlying mechanisms. METHODS: In in vivo experiments, adult male Sprague-Dawley 
      rats (12-week old) were used to induce acute focal cerebral ischemia employing 
      the middle cerebral artery occlusion (MCAO) method. In in vitro experiments, 
      postnatal day 1 (P1) Sprague-Dawley rat pups were used to prepare cultures of 
      primary astrocytes. Oxygen-glucose deprivation (OGD) and re-oxygenation (OGD/R) 
      procedures were employed to mimic the hypoxic-ischemic condition of stroke in 
      those astrocytes. RESULTS: We found in the peri-infarct area of the ipsilateral 
      cortex and striatum in Sprague-Dawley rats after transient MCAO an increase in 
      Pnn expression that correlated positively with the time-course of infarction as 
      detected by T2-weighted imaging and triphenyltetrazolium chloride staining, 
      augmented number of reactive astrocytes that double-labelled with Pnn as 
      determined by immunofluorescence, and enhanced cytotoxic edema as revealed by 
      diffusion weighted imaging; but mirrored the decreased cleaved caspase-3 as 
      measured by western blot. In an OGD and OGD/R model using primary cultured 
      astrocytes, treatment with Pnn siRNA doubled the chance of surviving astrocytes 
      to manifest cell death as revealed by flow cytometry, and blunted activated ERK 
      signaling, reduced Bcl-2 expression and augmented cleaved caspase 3 detected by 
      western blot in the normoxia, OGD or OGD/R group. Gene-knockdown of Pnn also 
      impeded the reversal from decline in cell viability, elevation in lactate 
      dehydrogenase leakage and decrease in ATP production in the OGD/R group. 
      CONCLUSION: We conclude that the endogenous Pnn participates in neuroprotection 
      after acute ischemic stroke by preserving the viability of astrocytes that 
      survived the ischemic challenge via maintenance of mitochondrial anti-apoptotic 
      and bioenergetics functions.
FAU - Mukda, Sujira
AU  - Mukda S
AD  - Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol 
      University, 25/25 Phuttamonthon 4 Road, Salaya, Nakhon Pathom, 73170, Thailand.
AD  - Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung 
      Memorial Hospital, 123 Dapi Rd, Kaohsiung, 83301, Taiwan.
FAU - Tsai, Ching-Yi
AU  - Tsai CY
AD  - Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung 
      Memorial Hospital, 123 Dapi Rd, Kaohsiung, 83301, Taiwan.
FAU - Leu, Steve
AU  - Leu S
AD  - Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung 
      Memorial Hospital, 123 Dapi Rd, Kaohsiung, 83301, Taiwan.
FAU - Yang, Jenq-Lin
AU  - Yang JL
AD  - Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung 
      Memorial Hospital, 123 Dapi Rd, Kaohsiung, 83301, Taiwan.
FAU - Chan, Samuel H H
AU  - Chan SHH
AUID- ORCID: 0000-0003-0028-5221
AD  - Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung 
      Memorial Hospital, 123 Dapi Rd, Kaohsiung, 83301, Taiwan. 
      shhchan@adm.cgmh.org.tw.
LA  - eng
GR  - CMRPG8E1421-3/Chang Gung Medical Foundation/
GR  - OMRPG8C0021/Chang Gung Medical Foundation/
PT  - Journal Article
DEP - 20190605
PL  - England
TA  - J Biomed Sci
JT  - Journal of biomedical science
JID - 9421567
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Pnn protein, rat)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics/*physiology
MH  - Apoptosis Regulatory Proteins/genetics/*physiology
MH  - Astrocytes/*pathology
MH  - Brain Ischemia/*pathology
MH  - Cell Adhesion Molecules/genetics/*physiology
MH  - Cell Death/genetics/physiology
MH  - Cell Survival
MH  - Male
MH  - Mitochondria/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stroke/*pathology
PMC - PMC6549339
OTO - NOTNLM
OT  - Cytotoxic edema
OT  - Middle cerebral artery occlusion
OT  - Oxygen-glucose deprivation
OT  - Peri-infarct area
OT  - Primary cultured astrocytes
COIS- The authors declared that they have no competing interests.
EDAT- 2019/06/07 06:00
MHDA- 2019/12/04 06:00
PMCR- 2019/06/05
CRDT- 2019/06/07 06:00
PHST- 2019/03/07 00:00 [received]
PHST- 2019/05/26 00:00 [accepted]
PHST- 2019/06/07 06:00 [entrez]
PHST- 2019/06/07 06:00 [pubmed]
PHST- 2019/12/04 06:00 [medline]
PHST- 2019/06/05 00:00 [pmc-release]
AID - 10.1186/s12929-019-0538-5 [pii]
AID - 538 [pii]
AID - 10.1186/s12929-019-0538-5 [doi]
PST - epublish
SO  - J Biomed Sci. 2019 Jun 5;26(1):43. doi: 10.1186/s12929-019-0538-5.