title: Extracellular signal-regulated kinase pathways may mediate the protective effect of electrical stimulation of the paraventricular nucleus against ischaemia-reperfusion injury of the gastric mucosa.
abstract: 1. The aim of the present study was to elucidate the role of the extracellular signal-regulated kinase (ERK) pathway in mediating the effects of electrical stimulation of the paraventricular nucleus (PVN) on apoptosis and proliferation induced by gastric ischaemia-reperfusion injury (GI/RI). 2. To investigate the effects of electrical stimulation of the hypothalamic PVN on gastric mucosal apoptosis and proliferation in response to ischaemia-reperfusion (I/R), we used a GI/RI model by clamping the coeliac artery for 30 min and then reperfusing the artery for 30 min or 1, 3 or 6 h. We used immunohistochemistry and western blotting to investigate the expression, activation and distribution of ERKs and the dynamic changes in their downstream cellular factors Bcl-2 and Bax at different times subsequent to electrical stimulation of the PVN in the I/R-injured gastric mucosa. 3. Electrical stimulation of the PVN markedly attenuated GI/RI at 30 min and 1 and 3 h after reperfusion. Electrical stimulation decreased gastric mucosal apoptosis, increased gastric mucosal proliferation and promoted the expression and activation of phosphorylated (p)-ERK1/2 30 min after reperfusion. Electrical stimulation increased the expression of Bcl-2 and decreased the expression of Bax at 30 min and 1 and 3 h after reperfusion. In contrast, inhibition of ERK1/2 activity by the specific upstream mitogen-activated protein kinase kinase inhibitor PD98059 produced similar effects at 1 h after reperfusion in rats subjected to I/R with or without electrical stimulation of the PVN. Administration of PD98059 aggravated gastric mucosal injury, increased apoptosis, decreased proliferation in gastric mucosal cells, decreased the expression and activity of p-ERK1/2 and Bcl-2 expression and increased Bax expression. 4. These results indicate that the PVN protects against GI/RI and that this protection is associated with the inhibition of cellular apoptosis and the promotion of proliferation in the gastric mucosa, probably by activating the ERK pathway.
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhang
authors.forename: Er-Qing
authors.initials: EQ
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Qiao
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Jian-Fu
authors.initials: JF
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002445:Celiac Artery / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005419:Flavonoids / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology / Q000294:innervation / Q000378:metabolism* / Q000473:pathology; D008026:Ligation; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000503:physiopathology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one