Granulocyte-colony stimulating factor protects against endoplasmic reticulum stress in an experimental model of stroke

Janet M. Menzie-Suderam, Payam Mohammadgharibani, Jigar Modi, Zea Ma, Rui Tao, Howard Prentice, Jang Yen Wu

Research output: Contribution to journalArticle

Abstract

Granulocyte-colony stimulating factor (G-CSF) is an endogenous growth factor that exhibits a diverse range of neuroprotective mechanisms against a variety of neurological disorders including ischemic stroke. We investigated the anti-apoptotic mechanisms of G-CSF against endoplasmic reticulum (ER) stress induced apoptosis. Sprague-Dawley rats were subjected to transient occlusion of the middle cerebral artery (MCAO) for 90 min. Rats were injected with G-CSF (n = 15; 50 μg/kg body weight s.c.) for 4 days, starting 24 h post-MCAO and brains were harvested after 4 days reperfusion (n = 16). Key proteins in ER stress apoptosis were analyzed by immunoblotting. G-CSF reduced infarct volume to 53% and improved neurological deficits. G-CSF treatment significantly (P <.05) attenuated the expression of proteins involved in ER stress apoptosis pathway; ATF4, ATF6, p-p38MAPK, pJNK and CHOP. G-CSF treatment also re-established ER homeostasis evident by the reduction of the intraluminal ER stress sensor, GRP78 as well as reducing the overall cellular stress level protein, HSP27. G-CSF also up-regulated anti-apoptotic proteins pAKT and Bcl-2 while down-regulated the pro-apoptotic protein Bax. G-CSF exerts neuroprotection from cerebral ischemia through the preservation of the ER, resulting in the attenuation of pro-apoptotic proteins and the potentiation of anti-apoptotic proteins.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalBrain research
Volume1682
DOIs
StatePublished - Mar 1 2018

Keywords

  • Endoplasmic reticulum stress apoptosis
  • Granulocyte-colony stimulating factor (G-CSF)
  • Neuroprotection
  • Stroke
  • Transient focal cerebral ischemia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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