Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:kappa-Opioid receptor potentiates apoptosis via a phospholipase C pathway in the CNE2 human epithelial tumor cell line. 1111 38

Se-methylselenocysteine (MSC) inhibits mouse mammary epithelial tumor cell (TM6) growth. When synchronized TM6 cells were exposed to 50 microM MSC, either for 30 minutes or continuous, the 116 kDa poly(ADP-ribose)polymerase (PARP) was cleaved to an 85 kDa fragment indicative of cells undergoing apoptosis. The earliest cleaved PARP appears at 24 hr time point followed by elevated levels of 85 kDa fragment at 34 hr and 48 hr time points when the cells were exposed to continuous treatment with MSC. Results also showed that MSC increased caspase-3 activity at 24 hr time point. In addition, continuous treatment with MSC induced DNA fragmentation at 34 hr and 48 hr time points with caspase-3 gene expression moderately increased at 16 hr and 24 hr time points. Caspase-6 and -8 were also involved in the MSC-induced apoptosis but to a lesser extent. These results suggest that MSC mediates cleavage of PARP and apoptosis by activating one or more caspases in synchronized TM6 cells and the events are dependent on the duration of treatment.
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PMID:Se-methylselenocysteine activates caspase-3 in mouse mammary epithelial tumor cells in vitro. 1156 54