The requirement of extracellular signal-related protein kinase pathway in the activation of hypoxia inducible factor 1 alpha in the developing rat brain after hypoxia-ischemia

Acta Neuropathologica
Lihua LiDezhi Mu

Abstract

Hypoxia inducible factor 1 alpha (HIF-1 alpha) is a key regulator of cellular oxygen homeostasis. However, the regulation of HIF-1 alpha in neonates with hypoxia-ischemia (HI) is not clear. Under normoxic conditions, the extracellular signal-related protein kinase (ERK) pathway has been shown to be involved in the activation of HIF-1 alpha in cell lines. Therefore, we hypothesized that the ERK pathway is involved in the activation of HIF-1 alpha and its target genes in the developing rat brain following HI. To test this hypothesis, we set up an HI model by ligating the right common carotid artery followed by hypoxia using postnatal day 10 rats. Rat brains from HI and sham controls were collected to detect the expression of HIF-1 alpha, its target gene, vascular endothelial growth factor (VEGF), and ERK using immunohistochemistry, Western blot analysis, and RT-PCR. We found that the expression of HIF-1 alpha protein was significantly upregulated at 4 h and peaked at 8 h after HI compared with sham controls. Accordingly, VEGF was similarly upregulated. However, the expression of total ERK (Erk1/2) had no obvious changes. Even though the phosphorylated form of ERK, p-Erk1/2, was upregulated and peaked at 4 h after HI, it is earlie...Continue Reading

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Citations

Jan 26, 2012·Neurotoxicity Research·Li ZhangDezhi Mu
Dec 2, 2010·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Liping CaiLiang Peng
Jan 17, 2009·Kidney International·Ichiro KojimaMasaomi Nangaku
Aug 11, 2011·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Jiao LiDezhi Mu
Aug 26, 2016·Reviews in the Neurosciences·Lan HuangDezhi Mu
Feb 27, 2015·Reviews in the Neurosciences·Haiting LiuDezhi Mu
Sep 4, 2009·American Journal of Physiology. Renal Physiology·Elke HammerschmidtGunter Wolf
Jan 17, 2021·Pediatrics International : Official Journal of the Japan Pediatric Society·Yoshiaki Sato, Masahiro Tsuji

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