IGF-I neuroprotection in the immature brain after hypoxia-ischemia, involvement of Akt and GSK3β?

Autor:	Anna-Lena Leverin, Carina Mallard, Jörgen Isgaard, Katarina G Brywe, Xiaoyang Wang, Maj Hedtjärn, Malin Gustavsson, Henrik Hagberg, Klas Blomgren
Rok vydání:	2005
Předmět:	medicine.medical_specialty Brain damage Protein Serine-Threonine Kinases Biology Neuroprotection Glycogen Synthase Kinase 3 GSK-3 Neurotrophic factors Proto-Oncogene Proteins Internal medicine medicine Animals Humans Insulin-Like Growth Factor I Rats Wistar Protein kinase B PI3K/AKT/mTOR pathway Glycogen Synthase Kinase 3 beta Kinase General Neuroscience Brain Rats Neuroprotective Agents Endocrinology Animals Newborn Apoptosis Hypoxia-Ischemia Brain medicine.symptom Proto-Oncogene Proteins c-akt
Zdroj:	European Journal of Neuroscience. 21:1489-1502
ISSN:	1460-9568 0953-816X
DOI:	10.1111/j.1460-9568.2005.03982.x
Popis:	Insulin-like growth factor I (IGF-I) is a neurotrophic factor that promotes neuronal growth, differentiation and survival. Neuroprotective effects of IGF-I have previously been shown in adult and juvenile rat models of brain injury. We wanted to investigate the neuroprotective effect of IGF-I after hypoxia-ischemia (HI) in 7-day-old neonatal rats and the mechanisms of IGF-I actions in vivo. We also wanted to study effects of HI and/or IGF-I on the serine/threonine kinases Akt and glycogen synthase kinase 3beta (GSK3beta) in the phophatidylinositol-3 kinase (PI3K) pathway. Immediately after HI, phosphorylated Akt (pAkt) and phosphorylated GSK3beta (pGSK3beta) immunoreactivity was lost in the ipsilateral and reduced in the contralateral hemisphere. After 45 min, pAkt levels were restored to control values, whereas pGSK3beta remained low 4 h after HI. Administration of IGF-I (50 microg i.c.v.) after HI resulted in a 40% reduction in brain damage (loss of microtubule-associated protein) compared with vehicle-treated animals. IGF-I treatment without HI was shown to increase pAkt whereas pGSK3beta decreased in the cytosol, but increased in the nuclear fraction. IGF-I treatment after HI increased pAkt in the cytosol and pGSK3beta in both the cytosol and the nuclear fraction in the ipsilateral hemisphere compared with vehicle-treated rats, concomitant with a reduced caspase-3- and caspase-9-like activity. In conclusion, IGF-I induces activation of Akt during recovery after HI which, in combination with inactivation of GSK3beta, may explain the attenuated activation of caspases and reduction of injury in the immature brain.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41f1c95eae7b8e9da7d0bdb77ef98d47 https://doi.org/10.1111/j.1460-9568.2005.03982.x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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