PMID- 31514228 OWN - NLM STAT- MEDLINE DCOM- 20210507 LR - 20211204 IS - 1440-1681 (Electronic) IS - 0305-1870 (Linking) VI - 47 IP - 2 DP - 2020 Feb TI - KIF2 mediates the neuroprotection in cerebral ischaemia injury by affecting NF-kappaB pathway. PG - 274-280 LID - 10.1111/1440-1681.13175 [doi] AB - 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 (KIF2) in the neuroprotection after cerebral I/R injury. KIF2 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, KIF2 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 KIF2 siRNA 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 KIF2 silencing. Furthermore, we found that the nuclear factor-kappa B (NF-kappaB) pathway was involved in KIF2-mediated neuroprotection after cerebral I/R injury, and induced apoptosis of hypoxic SK-N-SH cells by KIF2 silencing could be attenuated by the specific inhibitor BAY11-7082 of NF-kappaB. In conclusion, we demonstrate that KIF2 could mediate the neuroprotection in cerebral I/R injury by inhibiting activation of NF-kappaB pathway. This might provide a novel therapeutic target for cerebral I/R injury. CI - (c) 2019 John Wiley & Sons Australia, Ltd. FAU - Wang, Jin AU - Wang J AUID- ORCID: 0000-0002-5900-2954 AD - Department of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China. AD - Department of Encephalopathy, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, China. FAU - Chen, Jie AU - Chen J AD - Department of Encephalopathy, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, China. FAU - Chen, Jun AU - Chen J AD - Department of Encephalopathy, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, China. FAU - Liu, Xifang AU - Liu X AD - Nerve & Spine Ward, Rehabilitation Center for TCM Orthopedics, Xi'an Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China. FAU - Yang, Haixia AU - Yang H AD - Department of Encephalopathy, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, China. FAU - Liu, Jing AU - Liu J AD - Department of Encephalopathy, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, China. FAU - He, Ali AU - He A AD - Department of Acupuncture, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, China. FAU - Gao, Xiaohang AU - Gao X AD - Department of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China. FAU - Xin, Yinhu AU - Xin Y AD - Department of Encephalopathy, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191007 PL - Australia TA - Clin Exp Pharmacol Physiol JT - Clinical and experimental pharmacology & physiology JID - 0425076 RN - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile) RN - 0 (KIF2A protein, human) RN - 0 (NF-kappa B) RN - 0 (Nitriles) RN - 0 (Sulfones) RN - EC 3.6.4.4 (Kinesins) SB - IM MH - Animals MH - Brain Ischemia/*metabolism/prevention & control MH - Cell Line, Tumor MH - Humans MH - Kinesins/*biosynthesis MH - Male MH - NF-kappa B/antagonists & inhibitors/*metabolism MH - Neuroprotection/drug effects/*physiology MH - Nitriles/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Reperfusion Injury/*metabolism/prevention & control MH - Signal Transduction/drug effects/*physiology MH - Sulfones/pharmacology OTO - NOTNLM OT - KIF2 OT - NF-kappaB pathway OT - apoptosis OT - cerebral I/R injury OT - oxidative stress EDAT- 2019/09/13 06:00 MHDA- 2021/05/08 06:00 CRDT- 2019/09/13 06:00 PHST- 2018/08/30 00:00 [received] PHST- 2019/09/05 00:00 [revised] PHST- 2019/09/06 00:00 [accepted] PHST- 2019/09/13 06:00 [pubmed] PHST- 2021/05/08 06:00 [medline] PHST- 2019/09/13 06:00 [entrez] AID - 10.1111/1440-1681.13175 [doi] PST - ppublish SO - Clin Exp Pharmacol Physiol. 2020 Feb;47(2):274-280. doi: 10.1111/1440-1681.13175. Epub 2019 Oct 7.