| Autor: |
Diao CT; Department of Biochemistry, Faculty of Medicine, University of Hong Kong, PR China., Li L, Lau SY, Wong TM, Wong NS |
| Jazyk: |
angličtina |
| Zdroj: |
Biochimica et biophysica acta [Biochim Biophys Acta] 2000 Dec 11; Vol. 1499 (1-2), pp. 49-62. |
| DOI: |
10.1016/s0167-4889(00)00107-5 |
| Abstrakt: |
The mechanism by which kappa-opioid receptor (kappaor) modulated apoptosis was investigated in CNE2 human epithelial tumor cells. Induction of these cells to undergo apoptosis with staurosporine was associated with a massive increase in intracellular cAMP level. The inhibition of the increase in cAMP partially inhibited apoptosis as evidenced by a reduction of PARP and caspase-3 cleavage. Accordingly, a low but significant level of apoptosis is induced in these cells by the elevation of cAMP through the addition of forskolin and isobutylmethylxanthine. The existence of a cAMP-dependent and a cAMP-independent apoptotic pathway is therefore suggested. Receptor binding studies, RT-PCR experiments and Western blot analysis demonstrated the presence of type 1 kappaor in the CNE2 cells. Stimulation of kappaor in these cells resulted in the production of inositol (1,4,5)-trisphosphate, reduction of cAMP level and a marked enhancement of staurosporine-induced apoptosis. The potentiation of apoptosis by kappaor was prevented by inhibition of phospholipase C but was slightly enhanced by the presence of the active cAMP analogues, 8-CPT-cAMP and dibutyryl-cAMP. These data demonstrate for the first time that the phospholipase C pathway activated by type 1 kappaor expressed by cancer cells is involved in the potentiation of apoptosis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
