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Uncoupling Protein 2 Deficiency Enhances NLRP3 Inflammasome Activation Following Hyperglycemia-Induced Exacerbation of Cerebral Ischemia and Reperfusion Damage In Vitro and In Vivo
- Source :
- Neurochemical Research
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Mitochondrial uncoupling protein 2 (UCP2) deficiency exacerbates brain damage following cerebral ischemia/reperfusion (I/R). The Nod-like receptor protein-3 (NLRP3) inflammasome also plays a vital role in cerebral I/R damage. However, the effect of UCP2 on NLRP3 inflammasome-mediated hyperglycemia and I/R damage is not clear. In the present study, UCP2-knockout (UCP2−/−) and wild-type (WT) mice were used to establish a model of middle cerebral artery occlusion (MCAO) and reperfusion under normo- and hyperglycemic conditions. HT22 cells were established as a model of oxygen–glucose deprivation and reoxygenation (OGD/R) with high glucose to mimic hyperglycemia and I/R in vitro. HT22 cells were treated with/without different concentrations of the UCP2-specific inhibitor genipin for different periods of time. The results showed that UCP2 deficiency significantly increased histopathological changes and apoptosis after cerebral I/R damage in hyperglycemic mice. Moreover, UCP2 deficiency enhanced NLRP3 inflammasome activation in neurons when cerebral I/R damage was exacerbated by hyperglycemia. Furthermore, UCP2 deficiency enhanced NLRP3 inflammasome activation and reactive oxygen species (ROS) production in HT22 cells under OGD/R and high-glucose conditions. UCP2 deficiency aggravated hyperglycemia-induced exacerbation of cerebral I/R damage. UCP2 deficiency also enhanced NLRP3 inflammasome activation and ROS production in neurons in vitro and in vivo. These findings suggest that UCP2 deficiency enhances NLRP3 inflammasome activation following hyperglycemia-induced exacerbation of cerebral I/R damage in vitro and in vivo. UCP2 may be a potential therapeutic target for hyperglycemia-induced exacerbation of cerebral I/R damage.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Exacerbation
Inflammasomes
Ischemia
Apoptosis
Brain damage
Biochemistry
Cell Line
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
In vivo
Internal medicine
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Hypoxia
Receptor
Mice, Knockout
Neurons
chemistry.chemical_classification
Original Paper
Reactive oxygen species
Chemistry
Brain
Nod-like receptor protein-3
Infarction, Middle Cerebral Artery
Inflammasome
General Medicine
Cerebral ischemia
medicine.disease
Uncoupling protein 2
Mice, Inbred C57BL
Glucose
030104 developmental biology
Endocrinology
Hyperglycemia
Reperfusion Injury
Female
medicine.symptom
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 15736903 and 03643190
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Neurochemical Research
- Accession number :
- edsair.doi.dedup.....d4616aa50909f2fd60b40be51b8f3593