Preconditioning of H2S inhalation protects against cerebral ischemia/reperfusion injury by induction of HSP70 through PI3K/Akt/Nrf2 pathway

Kangxiang Ji; Long Xue; Jiwei Cheng; Yu Bai

doi:10.1016/j.brainresbull.2015.12.007

Preconditioning of H2S inhalation protects against cerebral ischemia/reperfusion injury by induction of HSP70 through PI3K/Akt/Nrf2 pathway

Brain Res Bull. 2016 Mar:121:68-74. doi: 10.1016/j.brainresbull.2015.12.007. Epub 2016 Jan 6.

Authors

Kangxiang Ji¹, Long Xue², Jiwei Cheng¹, Yu Bai³

Affiliations

¹ Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
² Department of Neurosurgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China.
³ Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. Electronic address: YuBai_Neurology@126.com.

PMID: 26772627
DOI: 10.1016/j.brainresbull.2015.12.007

Abstract

It is of great importance to protect the brain against cerebral ischemia and reperfusion (I/R) injury, which leads to excitotoxicity, redox imbalance, inflammation and apoptosis; however, there is currently no effective treatment. The present study aimed to investigate the effect of H2S preconditioning on cerebral I/R injury and its underlying mechanism. The results demonstrated that H2S preconditioning significantly prevented the development of neurological function abnormality, inflammation and oxidative injury in mice as well as cognitive impairment caused by cerebral I/R. H2S preconditioning also suppressed the apoptosis caused by cerebral I/R. Moreover, the protective effect of H2S preconditioning was found to involve heat shock protein 70 (HSP70), in which the PI3K/Akt/Nrf2 pathway was involved. The data showed that H2S preconditioning could protect mice against cerebral I/R injury by the induction of HSP70 and the PI3K/Akt/Nrf2 pathway.

Keywords: Akt; H(2)S; HSP70; Ischemia-reperfusion; Nrf2; PI3K.

MeSH terms

8-Hydroxy-2'-Deoxyguanosine
Administration, Inhalation
Animals
Brain Infarction / etiology
Brain Infarction / prevention & control
Deoxyguanosine / analogs & derivatives
Deoxyguanosine / metabolism
Disease Models, Animal
Enzyme Inhibitors / pharmacology
HSP70 Heat-Shock Proteins / metabolism*
Hydrogen Sulfide / administration & dosage
Hydrogen Sulfide / pharmacology*
Interleukin-6 / metabolism
Male
Malondialdehyde / metabolism
Maze Learning / physiology
Maze Learning / radiation effects
Mice
Mice, Inbred C57BL
Mice, Transgenic
NF-E2-Related Factor 2 / deficiency*
NF-E2-Related Factor 2 / genetics
Neurologic Examination
Oncogene Protein v-akt / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Reperfusion Injury / metabolism
Reperfusion Injury / prevention & control*
Signal Transduction / drug effects*
Tumor Necrosis Factor-alpha / metabolism

Substances

Enzyme Inhibitors
HSP70 Heat-Shock Proteins
Interleukin-6
NF-E2-Related Factor 2
Nfe2l2 protein, mouse
Tumor Necrosis Factor-alpha
Malondialdehyde
8-Hydroxy-2'-Deoxyguanosine
Oncogene Protein v-akt
Deoxyguanosine
Hydrogen Sulfide