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KIF 2 mediates the neuroprotection in cerebral ischaemia injury by affecting NF ‐κB pathway
Author(s) -
Wang Jin,
Chen Jie,
Chen Jun,
Liu Xifang,
Yang Haixia,
Liu Jing,
He Ali,
Gao Xiaohang,
Xin Yinhu
Publication year - 2020
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13175
Subject(s) - neuroprotection , pharmacology , gene knockdown , gene silencing , apoptosis , reactive oxygen species , superoxide dismutase , glutathione peroxidase , ischemia , chemistry , medicine , biology , oxidative stress , biochemistry , gene
Stroke is the most common cerebrovascular disease with high morbidity and mortality around the world. However, the underlying mechanisms involved in nerve injury and cerebral ischaemia/reperfusion (I/R) during cerebrovascular disease are still not completely clear. In the present study, we investigate the role of kinesin family member 2 ( KIF 2) in the neuroprotection after cerebral I/R injury. KIF 2 was aberrantly expressed in the cerebral tissues from middle cerebral artery occlusion ( MCAO ) rat model in a time dependent manner. A similar changing pattern was found in the cultured hypoxic neurons as well as SK ‐N‐ SH cells in vitro. Compared to the control, KIF 2 inhibition significantly increased the level of malonic dialdehyde ( MDA ), and reduced the level of superoxide dismutase ( SOD ) as well as glutathione peroxidase (GSH‐px) activity in cerebral tissues of MCAO rat model. The reactive oxygen species ( ROS ) level was also up‐regulated after KIF 2 si RNA knockdown in cultured hypoxic SK ‐N‐ SH cells. The apoptosis rates of hypoxic neurons and SK ‐N‐ SH cells as well as activated‐caspase‐3 level were obviously increased after KIF 2 silencing. Furthermore, we found that the nuclear factor‐kappa B ( NF ‐κB) pathway was involved in KIF 2‐mediated neuroprotection after cerebral I/R injury, and induced apoptosis of hypoxic SK ‐N‐ SH cells by KIF 2 silencing could be attenuated by the specific inhibitor BAY 11‐7082 of NF ‐κB. In conclusion, we demonstrate that KIF 2 could mediate the neuroprotection in cerebral I/R injury by inhibiting activation of NF ‐κB pathway. This might provide a novel therapeutic target for cerebral I/R injury.