[Effect of adrenocorticotropic hormone on the caspase-3 level and DNA fragmentation in hyperplasia tissue of human adrenals].
The effect of corticotropin and inhibitor of protein kinase C, chelerythrine chloride, on the change of caspase-3 level and on the rate of DNA laddering in hyperplasia adrenal cortex tissue of patient with Cushing's syndrome was studied. It was established that ACTH caused significant antiapoptotic effect in the human adrenal cortex. The adding of ACTH to incubation medium caused a sharp decrease of the caspase-3 level in adrenocorticocytes. Chelerythrine chloride, on the contrary, increases the caspase-3 level by 22%. ACTH influence decreases DNA laddering. Either the adding of chelerythrine chloride to incubation medium, or the adding of chelerythrine chloride simultaneously with ACTH, led to the enhancing of DNA fragmentation. The obtained data suggest that antiapoptotic effect of ACTH in adrenal cortex tissue estimated according by the caspase-3 level and by the rate of DNA fragmentation depends on activation of protein kinase C. However, the intensification of DNA laddering can be also explained by cytotoxic effect, high level of interaction with DNA and strong intercalation ability of this alkaloid.
Kovzun
O I
OI
Kostiuchenko
N M
NM
Mykosha
O S
OS
D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053119:Benzophenanthridines / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism*; D003470:Culture Media; D003480:Cushing Syndrome / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects*; D006801:Humans; D006965:Hyperplasia; D011493:Protein Kinase C / Q000378:metabolism
D000470:Alkaloids; D053119:Benzophenanthridines; D003470:Culture Media; D000324:Adrenocorticotropic Hormone; C016299:chelerythrine; D011493:Protein Kinase C; D053148:Caspase 3