Remote ischemic conditioning attenuates oxidative stress and inflammation via the Nrf2/HO-1 pathway in MCAO mice. 2023

Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
Stroke Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, Jilin, China.

The protective effects of remote ischemic conditioning (RIC) on acute ischemic stroke have been reported. However, the protective mechanisms of RIC have not been fully elucidated. This study aimed to investigate whether RIC could reduce oxidative stress and inflammatory responses in middle cerebral artery occlusion (MCAO)-reperfusion mice via the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. C57BL/6 mice were subjected to MCAO and underwent RIC twice daily at 1, 3, and 7 days after MCAO. ML385 was used to specifically inhibit Nrf2 in MCAO mice. Neurological deficit scores, infarct volume, and hematoxylin-eosin (HE) staining were assessed. Oxidative stress levels were assessed based on total antioxidant capacity (TAC), malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione/glutathione disulfide (GSH/GSSG). mRNA levels were detected using real-time polymerase chain reaction (PCR), and protein levels were detected using western blotting and enzyme-linked immunosorbent assay (ELISA). Protein localization was investigated using immunofluorescence staining. RIC significantly reduced infarct volume and improved neurological function and histological changes after MCAO. RIC significantly increased TAC, SOD, and GSH/GSSG levels and decreased MDA levels. RIC significantly increased Nrf2 and HO-1 mRNA levels and decreased Keap1, NLRP3, and Cleaved Caspase-1 mRNA levels. RIC significantly increased Nrf2, HO-1, and NQO1 protein expression and decreased Keap1, NLRP3, Cleaved Caspase-1, Cleaved IL-1β, IL-6, and TNF-α protein expression. RIC promoted the activation and translocation of Nrf2 into the nucleus. The protective effects of RIC were abolished by ML385 treatment. In conclusion, our findings suggest that RIC alleviates oxidative stress and inflammatory responses via the Nrf2/HO-1 pathway, which in turn improves neurobehavioral function. RIC may provide novel therapeutic options for acute ischemic stroke.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D000071199 NLR Family, Pyrin Domain-Containing 3 Protein An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME. Cold Autoinflammatory Syndrome 1 Protein,NACHT, LRR and PYD Domains-Containing Protein 3,NLRP3 Protein,NACHT, LRR and PYD Domains Containing Protein 3,NLR Family, Pyrin Domain Containing 3 Protein
D000072019 Kelch-Like ECH-Associated Protein 1 An adaptor protein characterized by an N-terminal BTB-POZ DOMAIN and six KELCH REPEATS that functions as a substrate for the E3 UBIQUITIN LIGASE complex. It negatively-regulates NF-E2-RELATED FACTOR 2 by targeting it for ubiquitination and degradation by the PROTEASOME. It also represses genes regulated by ANTIOXIDANT RESPONSE ELEMENTS. KEAP-1 Protein,KEAP1 Protein,KEAP 1 Protein,Kelch Like ECH Associated Protein 1
D000083242 Ischemic Stroke Stroke due to BRAIN ISCHEMIA resulting in interruption or reduction of blood flow to a part of the brain. When obstruction is due to a BLOOD CLOT formed within in a cerebral blood vessel it is a thrombotic stroke. When obstruction is formed elsewhere and moved to block a cerebral blood vessel (see CEREBRAL EMBOLISM) it is referred to as embolic stroke. Wake-up stroke refers to ischemic stroke occurring during sleep while cryptogenic stroke refers to ischemic stroke of unknown origin. Acute Ischemic Stroke,Cryptogenic Embolism Stroke,Cryptogenic Ischemic Stroke,Cryptogenic Stroke,Ischaemic Stroke,Wake-up Stroke,Acute Ischemic Strokes,Cryptogenic Embolism Strokes,Cryptogenic Ischemic Strokes,Cryptogenic Strokes,Embolism Stroke, Cryptogenic,Ischaemic Strokes,Ischemic Stroke, Acute,Ischemic Stroke, Cryptogenic,Ischemic Strokes,Stroke, Acute Ischemic,Stroke, Cryptogenic,Stroke, Cryptogenic Embolism,Stroke, Cryptogenic Ischemic,Stroke, Ischaemic,Stroke, Ischemic,Stroke, Wake-up,Wake up Stroke,Wake-up Strokes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000975 Antioxidants Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D051267 NF-E2-Related Factor 2 A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage. Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051547 Heme Oxygenase-1 A ubiquitous stress-responsive enzyme that catalyzes the oxidative cleavage of HEME to yield IRON; CARBON MONOXIDE; and BILIVERDIN. Hemeoxygenase 1,Heme Oxygenase 1,Oxygenase-1, Heme

Related Publications

Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
January 2022, Oxidative medicine and cellular longevity,
Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
January 2020, Oxidative medicine and cellular longevity,
Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
November 2017, Experimental and therapeutic medicine,
Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
September 2015, Basic & clinical pharmacology & toxicology,
Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
May 2023, Neurochemical research,
Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
July 2013, Hippocampus,
Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
June 2022, Molecular medicine reports,
Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
November 2022, Life sciences,
Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
January 2023, Molecular medicine reports,
Ying-Ying Sun, and Hong-Jing Zhu, and Ruo-Yu Zhao, and Sheng-Yu Zhou, and Mei-Qi Wang, and Yi Yang, and Zhen-Ni Guo
December 2023, European journal of pharmacology,
Copied contents to your clipboard!