Tat mediates apoptosis in vivo in the rat central nervous system.
The HIV-1 transactivator of transcription, Tat, mediates apoptosis in neurons and may cause AIDS-associated neurologic disorders, which include dementia and loss of motor control. Here we investigate the ability of Tat to stimulate apoptosis in the rat central nervous system in vivo. Using the TUNEL assay, treatment of rat pheochromocytoma (PC12) cells with 1.0 microgram/ml of Tat for 24 h was found to stimulate apoptosis. Further, electrophoresis of DNA from Tat-treated PC12 cells demonstrated fragmentation. To investigate Tat mediated apoptosis in vivo, 20 microgram of Tat was infused into the striatum of Sprague-Dawley rats. Histochemical analysis (TUNEL) of the Tat-infused area demonstrated apoptosis. Further, these rats demonstrated postural deviation ipsilateral to the infusion. These data demonstrate that Tat stimulates apoptosis in vivo and causes neurologic dysfunction in the intact animal.
Gavriil
E S
ES
Department of Biology, Adelphi University, Garden City, New York, 11530, USA.
Cooney
R
R
Weeks
B S
BS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D015696:Gene Products, tat / Q000008:administration & dosage / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D007263:Infusions, Parenteral; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity
D015696:Gene Products, tat; D011994:Recombinant Proteins