2. Academic Validation
  3. Suppression of mitochondrial fission in experimental cerebral ischemia: The potential neuroprotective target of p38 MAPK inhibition

Suppression of mitochondrial fission in experimental cerebral ischemia: The potential neuroprotective target of p38 MAPK inhibition

  • Neurochem Int. 2015 Nov;90:1-8. doi: 10.1016/j.neuint.2015.06.010.
Xue-Mei Zhang 1,  Li Zhang 2,  Guili Wang 3,  Wenxiu Niu 2,  Zhijie He 2,  Li Ding 2,  Jie Jia 4
Affiliations

Affiliations

  • 1 Department of Traditional Chinese and Western Medicine Combination, Henan Xinxiang Center Hospital, Henan Xinxiang 453000, China.
  • 2 Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China.
  • 3 Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China; College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, China.
  • 4 Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: [email protected].
PMID: 26116440 DOI: 10.1016/j.neuint.2015.06.010
Abstract

In the present study, we investigated the neuroprotective role of p38 inhibition on experimental stroke in rats. p38 inhibition treatment alleviated the brain infarction volume and neurological deficits following ischemia, promoted the activation of Extracellular signal-regulated kinases (ERK1/2), suppressed the activation of Glycogen synthase kinase 3 beta (GSK3b). Application of two p38 inhibitors, both SB239063 and Losmapimod could down-regulate DLP1 and MFF, which were involved in mitochondrial fission and fragmentation. Losmapimod application progressively suppressed DLP1/MFF from 6 h to 24 h after ischemia-reperfusion injury. SB239063 pretreatment further showed the suppression of DLP1/MFF, and up-regulated the protein levels of p62 and Mitochondrial Complex I at 5 mg/kg dose. Our results suggested that inhibition of p38 MAPK attenuated mitochondrial fragmentation/Mitophagy after ischemic attack. In conclusion, p38 inhibition treatment might promote cellular survival signaling pathways, attenuate mitochondrial Autophagy to maintain mitochondrial contents. This study suggests a potential neuroprotective target of p38 inhibition via suppressing mitochondrial fragmentation/Mitophagy in cerebral ischemic injury.

Keywords

Mitochondrial fission; Mitophagy; Neuroprotection; p38.

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