NF-κB Inhibitor Suppresses Hypoxia-induced Apoptosis of Mouse Pancreatic β-cell Line MIN6

Abstract

attempted to determine the potential usefulness of NF-κB inhibitor for suppression of hypoxia-induced β-cellapoptosis as well as the relationship between IP-10 induction and β-cell apoptosis in hypoxia. To accomplish this, wecultured the mouse pancreatic β-cell line MIN6 in hypoxia (1% O2). Among several examined chemokines, only IP-10mRNA expression was induced under hypoxia, and this induced IP-10 expression was due to NF-κB activity. Since aprevious study suggested that IP-10 mediates β-cell apoptosis, we measured hypoxia-induced IP-10 protein and examinedthe 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 relationshipbetween hypoxia-induced IP-10 mRNA expression and hypoxia-induced β-cell apoptosis. Since it was still not clear ifNF-κB functions as an apoptotic or anti-apoptotic mediator in hypoxia-induced β-cell apoptosis, we examined possibleinvolvement of NF-κB in hypoxia-induced β-cell apoptosis. Treatment with 1 μM NF-κB inhibitor suppressed hypoxiainducedapoptosis by more than 50%, while 10 μM AP-1 or 4 μM NF-AT inhibitor did not, indicating involvement ofNF-κB in hypoxia-induced β-cell apoptosis. Overall, these results suggest that IP-10 is not involved in hypoxia-inducedβ-cell apoptosis, and that NF-κB inhibitor can be useful for ameliorating hypoxia-induced β-cell apoptosis.