The effect of ursodeoxycholic acid on the survivin in thapsigargin-induced apoptosis.
Endoplasmic reticulum (ER) was recently suggested as a third subcellular compartment in apoptotic execution. Survivin is a member of inhibitors of apoptosis and ursodeoxycholic acid (UDCA) prevents apoptosis from various apoptotic stimuli. To assess the activity of survivin and the effect of UDCA on the survivin in ER stress-mediated apoptosis, we treated hepatoma cell lines with thapsigargin (TG). TG-induced apoptosis was assessed by morphological changes, DNA fragmentation, cleavages of poly(ADP-ribose)polymerase (PARP), and activation of calpain and caspase-12. The level of survivin was decreased after TG treatment in hepatoma cell lines indicating that survivin play an important role in ER stress-mediated apoptosis. UDCA prevented decrease in survivin levels and inhibited TG-induced apoptosis and caspase-12 activation suggesting an anti-apoptotic effect of UDCA.
Sohn
Joohyun
J
Department of Medicine, Baylor College of Medicine and Veterans Affairs Medical Center (151B), 2002 Holcombe Boulevard, Houston, TX 77030, USA.
Khaoustov
Vladimir I
VI
Xie
Qing
Q
Chung
Charles C
CC
Krishnan
Bhuvaneswari
B
Yoffe
Boris
B
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002154:Calpain / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D053454:Caspase 12; D020169:Caspases / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D019254:Genes, bcl-2; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D019284:Thapsigargin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D019284:Thapsigargin; D014580:Ursodeoxycholic Acid; D011065:Poly(ADP-ribose) Polymerases; C506444:CASP12 protein, human; D002154:Calpain; D053454:Caspase 12; D020169:Caspases