|
KMID : 0603820140200010014
|
|
Journal of Experimental & Biomedical Science
2014 Volume.20 No. 1 p.14 ~ p.24
|
|
|
NF-κB Inhibitor Suppresses Hypoxia-induced Apoptosis of Mouse Pancreatic β-cell Line MIN6
|
|
Koh Hyun-Sook
Kim Jae-Young
|
|
|
Abstract
|
|
|
|
Hypoxia is one of the main reasons for islet apoptosis after transplantation as well as during isolation. In this study, we attempted to determine the potential usefulness of NF-κB inhibitor for suppression of hypoxia-induced β-cell apoptosis as well as the relationship between IP-10 induction and β-cell apoptosis in hypoxia. To accomplish this, we cultured the mouse pancreatic β-cell line MIN6 in hypoxia (1% O₂). Among several examined chemokines, only IP-10 mRNA expression was induced under hypoxia, and this induced IP-10 expression was due to NF-κB activity. Since a previous study suggested that IP-10 mediates β-cell apoptosis, we measured hypoxia-induced IP-10 protein and examined the effect of anti-IP-10 neutralizing Ab on hypoxia-induced β-cell apoptosis. However, IP-10 protein was not detected, and anti-IP-10 neutralizing Ab did not rescue hypoxia-induced MIN6 apoptosis, indicating that there is no relationship between hypoxia-induced IP-10 mRNA expression and hypoxia-induced β-cell apoptosis. Since it was still not clear if NF-κB functions as an apoptotic or anti-apoptotic mediator in hypoxia-induced β-cell apoptosis, we examined possible involvement of NF-κB in hypoxia-induced β-cell apoptosis. Treatment with 1 μM NF-κB inhibitor suppressed hypoxiainduced apoptosis by more than 50%, while 10 μM AP-1 or 4 μM NF-AT inhibitor did not, indicating involvement of NF-κB in hypoxia-induced β-cell apoptosis. Overall, these results suggest that IP-10 is not involved in hypoxia-induced β-cell apoptosis, and that NF-κB inhibitor can be useful for ameliorating hypoxia-induced β-cell apoptosis.
|
|
|
KEYWORD
|
|
|
NF-kappaB, Cell hypoxia, Insulin-secreting cells, Apoptosis, Chemokine CXCL10
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|