TY - JOUR
T1 - Pituitary adenylate cyclase-activating polypeptide prevents cytokine-induced cytotoxicity via inhibition of inducible nitric oxide synthase expression in βTC cells
AU - Sekiya, Kayo
AU - Nagasaki, Hiroshi
AU - Ozaki, Nobuaki
AU - Suzuki, Atsushi
AU - Miura, Yoshitaka
AU - Oiso, Yutaka
N1 - Funding Information:
This work was supported in part by the Research for the Future Program, The Japan Society for the Promotion of Science (JSPS-RFTF97I00201), and by a Grant-in Aid for Scientific Research (B) from the Ministry of Education, Science, Sports, and Culture, Japan (08457263). We are grateful to Dr. Douglas Hanahan and Dr. Ka-tsuhiko Yoshimoto for generously providing βTC cells, and to Dr. Ichiro Niki for helpful discussion of the manuscript.
PY - 2000/11/11
Y1 - 2000/11/11
N2 - Type 1 diabetes mellitus is an autoimmune disease resulting from apoptotic destruction of pancreatic β-cells. The activation of inducible nitric oxide synthase (iNOS) by inflammatory cytokines is considered a mediator of destruction in β-cells. Recent findings showed that the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP), whose distribution was identified in pancreatic neurons, inhibited nitric oxide (NO) production in cytokine-activated macrophages. In the present study, we investigated the cytoprotective effect of PACAP in the cytokine-exposed mice β-cell line, βTC cells. 1 x 10-8 M PACAP inhibited the reduction of cell viability, NO production, expression of iNOS mRNA, and iNOS promoter activity caused by the combination of three proinflammatory cytokines. Selective iNOS inhibitor also showed the cytoprotective effect in βTC cells. These data suggested that PACAP has a cytoprotective effect in cytokine-treated β-cells through inhibition of iNOS transcription. (C) 2000 Academic Press.
AB - Type 1 diabetes mellitus is an autoimmune disease resulting from apoptotic destruction of pancreatic β-cells. The activation of inducible nitric oxide synthase (iNOS) by inflammatory cytokines is considered a mediator of destruction in β-cells. Recent findings showed that the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP), whose distribution was identified in pancreatic neurons, inhibited nitric oxide (NO) production in cytokine-activated macrophages. In the present study, we investigated the cytoprotective effect of PACAP in the cytokine-exposed mice β-cell line, βTC cells. 1 x 10-8 M PACAP inhibited the reduction of cell viability, NO production, expression of iNOS mRNA, and iNOS promoter activity caused by the combination of three proinflammatory cytokines. Selective iNOS inhibitor also showed the cytoprotective effect in βTC cells. These data suggested that PACAP has a cytoprotective effect in cytokine-treated β-cells through inhibition of iNOS transcription. (C) 2000 Academic Press.
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U2 - 10.1006/bbrc.2000.3784
DO - 10.1006/bbrc.2000.3784
M3 - Article
C2 - 11071874
AN - SCOPUS:0034638615
SN - 0006-291X
VL - 278
SP - 211
EP - 216
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
