Cordycepin rapidly collapses the intermediate filament networks into juxtanuclear caps in fibroblasts and epidermal cells.
The nucleoside analog 3'-deoxyadenosine (cordycepin) rapidly collapses the intermediate filaments into juxtanuclear caps in interphase fibroblasts and keratinocytes. A minimum of 80 micrograms/ml cordycepin or 20 micrograms/ml cordycepin in combination with 2 micrograms/ml of the deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenosine (EHNA) to inhibit its degradation is required to see these effects. This is the same concentration required for cordycepin to arrest cells at the onset of mitosis and depolymerize the microtubules to small asters. Cordycepin enters the cells rapidly and is phosphorylated to 3'-dATP with a concomitant drop in ATP levels. However, the direct reduction of ATP levels does not mimic the same rapid effects of cordycepin on either the intermediate filaments or microtubules. In addition, similar effects are not produced by a variety of other adenosine analogs with alterations in the 2'- and 3'-ribose positions. Although other pharmacological reagents result in alterations of the fibroblastic intermediate filaments, cordycepin is unusual because of the rapidity with which the fibroblastic intermediate filaments collapse into the juxtanuclear caps. The juxtanuclear caps have a morphology different from that of the perinuclear bundles of intermediate filaments that arise after long-term depolymerization of the microtubules. The keratin fibers in the epidermal cells retract to a perinuclear ring when treated with cordycepin.
Zieve
G W
GW
Department of Anatomical Sciences, SUNY at Stony Brook 11794-8081.
Roemer
E J
EJ
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006224:Cricetinae; D003599:Cytoskeleton / Q000187:drug effects*; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D003839:Deoxyadenosines / Q000494:pharmacology*; D004817:Epidermis / Q000378:metabolism / Q000648:ultrastructure*; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure*; D007382:Intermediate Filaments / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007399:Interphase; D007633:Keratins / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D014746:Vimentin; D014638:Vanadates; C010192:9-(2-hydroxy-3-nonyl)adenine; C011746:3'-deoxyadenosine 5'-triphosphate; D007633:Keratins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D000225:Adenine