Protective effect of Coptidis Rhizoma on S-nitroso-N-acetylpenicillamine (SNAP)-induced apoptosis and necrosis in pancreatic RINm5F cells.
Coptidis rhizoma (CR) is a herb used in many traditional prescriptions against diabetes mellitus in Asia for centuries. Our purpose was to determine the protective effect and its action mechanism of CR on the cytotoxicity of pancreatic beta-cells. Nitric oxide (NO) is believed to play a key role in the process of pancreatic beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM). Exposure of RINm5F cells to chemical NO donor such as S-nitroso-N-acetylpenicillamine (SNAP) induced apoptotic events such as the disruption of mitochondrial membrane potential (Deltapsim), cytochrome c release from mitochondria, activation of caspase-3, poly (ADP-ribose) polymerase cleavage and DNA fragmentation. Also, exposure of SNAP led to LDH release into medium, one of the necrotic events. However, pretreatment of RINm5F cells with CR extract protected both apoptosis and necrosis through the inhibition of Deltapsim disruption in SNAP-treated RINm5F cells. In addition, rat islets pretreated with CR extract retained the insulin-secretion capacity even after the treatment with IL-1beta. These results suggest that CR may be a candidate for a therapeutic or preventing agent against IDDM.
Kwon
Kang-Beom
KB
Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Chonbuk, 570-749, South Korea.
Kim
Eun-Kyung
EK
Lim
Jung-Gook
JG
Shin
Byung-Cheul
BC
Han
Sang-Chil
SC
Song
Bong-Keun
BK
Kim
Kang-San
KS
Seo
Eun-A
EA
Ryu
Do-Gon
DG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000089042:Coptis chinensis; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007340:Insulinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009336:Necrosis / Q000517:prevention & control*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; C107393:Coptidis rhizoma extract; D007770:L-Lactate Dehydrogenase; D010396:Penicillamine