Cerebral Ischemic Preconditioning Aggravates Death of Oligodendrocytes

Neurodegeneration can benefit from ischemic preconditioning, a natural adaptive reaction to sublethal noxious stimuli. Although there is growing interest in advancing preconditioning to preserve brain function, preconditioning is not yet considered readily achievable in clinical settings. One of the...

Full description

Saved in:
Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2022-12, Vol.12 (12), p.1872
Main Authors: Guan, Teng, Guo, Ying, Li, Chengren, Zhou, Ting, Yu, Qiang, Yang, Chaoxian, Zhang, Guohui, Kong, Jiming
Format: Article
Language:English
Subjects:
Bcl-2 protein
BNIP3 protein
Brain
Experiments
Gene expression
Glial stem cells
Growth factors
Health aspects
Ischemia
Ischemic Preconditioning
ischemic stroke
Metabolism
Mitochondria
Mitochondria - metabolism
Nervous system
Neurodegeneration
Oligodendrocytes
Oligodendroglia
Oligodendroglia - metabolism
Pain perception
Physiological aspects
Post traumatic stress disorder
preconditioning
RNA-mediated interference
Stroke
Stroke (Disease)
Substantia alba
Transient ischemic attack
Veins & arteries
White Matter
white matter injury
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Neurodegeneration can benefit from ischemic preconditioning, a natural adaptive reaction to sublethal noxious stimuli. Although there is growing interest in advancing preconditioning to preserve brain function, preconditioning is not yet considered readily achievable in clinical settings. One of the most challenging issues is that there is no fine line between preconditioning stimuli and lethal stimuli. Here, we show deleterious effect of preconditioning on oligodendrocyte precursor cells (OPCs). We identified Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), a mitochondrial BH3-only protein specifically involved in OPCs loss after preconditioning. Repeated ischemia stabilized BNIP3 and increased the vulnerability of OPCs to subsequent ischemic events. BNIP3 became mitochondrial-bound and was concurrent with the dysfunction of monocarboxylate transporter 1 (MCT1). Inhibition of BNIP3 by RNAi or necrostatin-1 (Nec-1) and knocking out of BNIP3 almost completely prevented OPCs loss and preserved white matter integrity. Together, our results suggest that the unfavorable effect of BNIP3 on OPCs should be noted for safe development of ischemic tolerance. BNIP3 inhibition appears to be a complementary approach to improve the efficacy of preconditioning for ischemic stroke.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom12121872