Neuregulin-1 regulates the expression of Akt, Bcl-2, and Bad signaling after focal cerebral ischemia in rats.
Neuregulin-1 (NRG-1) is a member of the epidermal growth factor family. Our previous study showed that NRG-1 protected neurons from apoptosis following focal cerebral ischemia by the inhibition of caspase-3 and TNF-alpha expression. However, the molecular signaling mechanisms for this action of NRG-1 following cerebral ischemia are not fully understood. Presently, activation of the PI3K/Akt pathway has been implicated as a major contributor to neuronal survival after an ischemic insult. In the present study, we investigated whether NRG-1 modulates the activation of Akt and its downstream targets Bad and Bcl-2 expression after transient focal cerebral ischemia by intraluminal blockade of the middle cerebral artery. Western blot was employed to analyze the change of phosphorylated Akt (p-Akt) expression; reverse transcription and polymerization chain reaction (RT-PCR) were used to measure changes of Bcl-2 mRNA. The level of phosphorylation of Bad (p-Bad) was determined using an enzyme-linked immunosorbent assay (ELISA). Our results showed that recombinant human NRG-1(3.0 ng.kg-1) significantly increased the expression of p-Akt protein, Bcl-2 mRNA, and the level of p-Bad, respectively, whereas administration of LY294002, a specific inhibitor of PI3K, significantly decreased the expression of p-Akt, p-Bad, and Bcl-2 induced by NRG-1 after a 60 min ischemic insult, followed by 24 h of reperfusion. These results indicate that NRG-1 may be involved in regulating the expression of Bcl-2 and p-Bad through the PI3K/Akt pathway after transient focal cerebral ischemia.
Guo
Wen-Ping
WP
Department of Anatomy, Medical College of Shantou University, Shantou, Guangdong, China. guowenping68@163.com
Fu
Xin-Ge
XG
Jiang
Su-Ming
SM
Wu
Jian-Zhong
JZ
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D020890:Neuregulin-1 / Q000494:pharmacology / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000235:genetics* / Q000378:metabolism
C494821:Bad protein, rat; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011994:Recombinant Proteins; D051025:bcl-Associated Death Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051058:Oncogene Protein v-akt