ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: We show here that 2′-deoxyadenosine (2′-dAdo) but not adenosine was toxic to chromaffin cells of 3–4-week-old rat adrenal glands. More than 75% of the cells plated in culture gradually died over a 3-day period in the presence of 100 µM 2′-dAdo plus 3 µM deoxycoformycin (DCF). Morphological observations together with bisbenzimide staining and terminal deoxynucleotidyl transferase-mediated nick end labeling showed membrane blebbing, shrinkage of cell bodies, chromatin condensation, and DNA fragmentation, suggesting apoptosis-like cell death by 2′-dAdo. Lethal effects of 2′-dAdo were potentiated by DCF, a drug that inhibits adenosine deaminase. 2′-dAdo-prompted cell death was not prevented by inhibitors of nucleoside transporter (3 µM dilazep or 1 µM nitrobenzylthioinosine), precursors of pyrimidine nucleotide biosynthesis (300 µM uridine or 100 µM 2′-deoxycytidine), or 5 mM nicotinamide. Cells incubated with 2′-dAdo (100 and 300 µM) showed a three- and ninefold, respectively, increase in content of dATP, a product known to be an inhibitor of ribonucleotide reductase, an enzyme essential for DNA synthesis. Formation of dATP was completely prevented by iodotubercidin (ITu), a drug that inhibits phosphorylation of 2′-dAdo to dATP by nucleoside kinase. It is interesting that nanomolar concentrations of ITu also completely protected chromaffin cells from 2′-dAdo lethality. Our study demonstrates for the first time that mammalian adrenal chromaffin cells undergo apoptotic cell death by a natural nucleoside and suggests that this model could be used to study apoptosis and cell function.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1996.67062273.x
