PMID- 31211943
OWN - NLM
STAT- MEDLINE
DCOM- 20200304
LR  - 20240229
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 320
DP  - 2019 Oct
TI  - EPO regulates neuroprotective Transmembrane BAX Inhibitor-1 Motif-containing 
      (TMBIM) family members GRINA and FAIM2 after cerebral ischemia-reperfusion 
      injury.
PG  - 112978
LID - S0014-4886(19)30130-X [pii]
LID - 10.1016/j.expneurol.2019.112978 [doi]
AB  - BACKGROUND AND PURPOSE: Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) 
      family members exert inhibitory activities in apoptosis and necroptosis. FAIM2 
      (TMBIM-2) is neuroprotective against murine focal ischemia and is regulated by 
      erythropoietin (EPO). Similar to FAIM2, GRINA (TMBIM-3) is predominantly 
      expressed in the brain. The role of GRINA in transient brain ischemia, its 
      potential synergistic effects with FAIM2 and its regulation by EPO treatment were 
      assessed. METHODS: We performed transient (30 min) middle cerebral artery 
      occlusion (tMCAo) followed by 72 h of reperfusion in GRINA-deficient 
      (GRINA(-/-)), FAIM2-deficient (FAIM2(-/-)), double-deficient 
      (GRINA(-/-)FAIM2(-/-)) and wildtype littermates (WT) mice. We administered EPO or 
      saline 0, 24 and 48 h after tMCAo. We subjected primary murine cortical neurons 
      (pMCN) of all mouse strains to oxygen-glucose deprivation (OGD) after GRINA 
      and/or FAIM2 gene transfection. RESULTS: Compared to wildtype controls GRINA 
      deficiency led to a similar increase in infarct volumes as FAIM2 deficiency 
      (p < .01). We observed the highest neurological deficits and largest infarct 
      sizes in double-deficient mice. EPO administration upregulated GRINA and FAIM2 
      mRNA levels in wildtype littermates. EPO decreased infarct sizes and abrogated 
      neurological impairments in wildtype controls. GRINA and/or FAIM2 deficient mice 
      showed increased expression levels of cleaved-caspase 3 and of pro-apoptotic BAX 
      mRNA. Further, caspase 8 was upregulated in FAIM2(-/-) and caspase 9 in 
      GRINA(-/-) mice. Overexpression of GRINA and FAIM2 in wildtype and in double 
      deficient pMCN decreased cell death rate after OGD. CONCLUSIONS: GRINA and FAIM2 
      are highly expressed in the brain and convey EPO-mediated neuroprotection after 
      ischemic stroke involving different caspases.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Habib, Pardes
AU  - Habib P
AD  - Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany. 
      Electronic address: phabib@ukaachen.de.
FAU - Stamm, Ann-Sophie
AU  - Stamm AS
AD  - Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany.
FAU - Zeyen, Thomas
AU  - Zeyen T
AD  - Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany.
FAU - Noristani, Rozina
AU  - Noristani R
AD  - Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany.
FAU - Slowik, Alexander
AU  - Slowik A
AD  - Institute of Neuroanatomy, Medical School, RWTH Aachen University, Aachen, 
      Germany.
FAU - Beyer, Cordian
AU  - Beyer C
AD  - Institute of Neuroanatomy, Medical School, RWTH Aachen University, Aachen, 
      Germany.
FAU - Wilhelm, Thomas
AU  - Wilhelm T
AD  - Institute of Biochemistry and Molecular Immunology, Medical School, RWTH Aachen 
      University, Aachen, Germany.
FAU - Huber, Michael
AU  - Huber M
AD  - Institute of Biochemistry and Molecular Immunology, Medical School, RWTH Aachen 
      University, Aachen, Germany.
FAU - Komnig, Daniel
AU  - Komnig D
AD  - Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany.
FAU - Schulz, Jorg B
AU  - Schulz JB
AD  - Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany; 
      JARA-BRAIN Institute of Molecular Neuroscience and Neuroimaging, 
      Forschungszentrum Julich GmbH and RWTH Aachen University, Aachen, Germany.
FAU - Reich, Arno
AU  - Reich A
AD  - Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190615
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 64FS3BFH5W (Epoetin Alfa)
RN  - 0 (Grina protein, mouse)
RN  - 0 (lifeguard protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
SB  - IM
MH  - Animals
MH  - Male
MH  - Mice
MH  - *Brain Ischemia/metabolism
MH  - *Epoetin Alfa/pharmacology
MH  - Infarction, Middle Cerebral Artery/metabolism/pathology
MH  - *Membrane Proteins/metabolism
MH  - Mice, Knockout
MH  - *Nerve Tissue Proteins/metabolism
MH  - Neuroprotective Agents/pharmacology
MH  - *Reperfusion Injury/metabolism/pathology
OTO - NOTNLM
OT  - Erythropoietin
OT  - MCAo
OT  - OGD, GRINA, FAIM2
OT  - Stroke
EDAT- 2019/06/19 06:00
MHDA- 2020/03/04 06:00
CRDT- 2019/06/19 06:00
PHST- 2019/05/02 00:00 [received]
PHST- 2019/06/03 00:00 [revised]
PHST- 2019/06/12 00:00 [accepted]
PHST- 2019/06/19 06:00 [pubmed]
PHST- 2020/03/04 06:00 [medline]
PHST- 2019/06/19 06:00 [entrez]
AID - S0014-4886(19)30130-X [pii]
AID - 10.1016/j.expneurol.2019.112978 [doi]
PST - ppublish
SO  - Exp Neurol. 2019 Oct;320:112978. doi: 10.1016/j.expneurol.2019.112978. Epub 2019 
      Jun 15.