Effect of atorvastatin on AGEs-induced injury of cerebral cortex via inhibiting NADPH oxidase -NF-κB pathway in ApoE−/− mice

Advanced glycation end products (AGEs) are a group of modified proteins and/or lipids with damaging potential. AGEs-RAGE pathway plays a critical role to induce neurodegenerative encephalopathy. Statins can reduce the expression of AGEs-induced AGEs receptor (RAGE) in the aorta. It is not clear whet...

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Bibliographic Details
Published in:Molecular biology reports 2020-12, Vol.47 (12), p.9479-9488
Main Authors: Li, Zhenhan, Yang, Peiye, Feng, Bo
Format: Article
Language:English
Subjects:
Advanced glycosylation end products
Alzheimer's disease
Amyloid beta-Peptides - genetics
Amyloid beta-Peptides - metabolism
Animal Anatomy
Animal Biochemistry
Animals
Anticholesteremic Agents - pharmacology
Aorta
Apolipoprotein E
Apolipoproteins
Apolipoproteins E - deficiency
Apolipoproteins E - genetics
Atorvastatin
Atorvastatin - pharmacology
Biomedical and Life Sciences
Brain
Cerebral cortex
Cerebral Cortex - drug effects
Cerebral Cortex - metabolism
Cerebral Cortex - pathology
Cognitive ability
Coronary vessels
Cytokines
Diabetes
Diet, High-Fat - adverse effects
Encephalopathy
Endocrinology
Ethanol
Gene Expression Regulation
Glucose
Glycation End Products, Advanced - genetics
Glycation End Products, Advanced - metabolism
Glycation End Products, Advanced - pharmacology
Glycosylation
Histology
Hospitals
Immunohistochemistry
Inflammation
Kinases
Laboratory animals
Life Sciences
Lipids
Male
Mice
Mice, Knockout
Molecular biology
Morphology
mRNA
NAD(P)H oxidase
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - genetics
NADPH Oxidases - metabolism
NADPH-diaphorase
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
NF-κB protein
Original Article
Oxidative stress
Oxidative Stress - drug effects
Polymerase chain reaction
Proteins
Receptor for Advanced Glycation End Products - genetics
Receptor for Advanced Glycation End Products - metabolism
Signal Transduction
Statins
Thiazoles - pharmacology
Transcription Factor RelA - antagonists & inhibitors
Transcription Factor RelA - genetics
Transcription Factor RelA - metabolism
Tumor necrosis factor-TNF
β-Amyloid
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Summary:Advanced glycation end products (AGEs) are a group of modified proteins and/or lipids with damaging potential. AGEs-RAGE pathway plays a critical role to induce neurodegenerative encephalopathy. Statins can reduce the expression of AGEs-induced AGEs receptor (RAGE) in the aorta. It is not clear whether statins have potential benefits on AGEs-induced cognitive impairment. In this study, the effects of atorvastatin (ATV) on inflammation and oxidation stress in the cerebral cortex were investigated, and the underlying mechanisms were explored. Apolipoprotein E (ApoE) −/− male mice were divided into four groups: control, AGEs, AGEs + ALT711 (Alagebrium chloride) and AGEs + ATV. β-amyloid (Aβ) formation in the cerebral cortex was assessed through Congo red staining and the functional state of neurons was evaluated by Nissl’s staining. Immunostaining was performed to assess the accumulation of AGEs in the cerebral cortex. The expressions of mRNA and protein of RAGE, Nuclear factor kappa B (NF-κB) p65 and Nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) p47phox were detected by real-time polymerase chain reaction (PCR) and western blot. There were significant increases in AGEs deposit, Aβ formation, and the expressions of RAGE, NF-κB p65, and NADPH oxidase p47phox, and a decrease Nissl body in AGEs group compared with control group. ALT711 group recovered above change compared with AGEs group. Atorvastatin reduced Aβ formation and suppressed AGEs-induced expressions of NF-κB p65 and NADPH oxidase p47phox. Atorvastatin has little effects on AGEs deposit and RAGE expressions. Atorvastatin alleviates AGEs-induced neuronal impairment by alleviating inflammation and oxidative stress via inhibiting NADPH oxidase-NF-κB pathway.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-020-05998-z