TGF-beta1 prevents gp120-induced impairment of Ca2+ homeostasis and rescues cortical neurons from apoptotic death.
HIV-1 infection frequently induces neuronal death responsible for the development of neurological deficits associated with AIDS. Several reports suggest that gp120, the HIV-1 envelope glycoprotein, is the main candidate as mediator of the HIV-1-dependent neurotoxicity. Here we report the effect of gp120 on the survival of cortical neurons in vitro and the possible mechanisms whereby it occurs. Mature cortical neurons, cultured on a feeder layer of astrocytes, were treated with gp120 in a defined culture medium in absence of serum. The treatment with gp120 induced time-dependent neuronal damage displaying apoptotic features, as revealed by in situ labelling of DNA fragmentation. TGF-beta1, a cytokine that has been previously shown to exert neuroprotective effects, prevented the cell death induced by exposure of cortical neurons to gp120. The prolonged treatment with gp120 also increased neuronal [Ca2+]i, while the coincubation with TGF-beta1 completely prevented the impairment of neuronal Ca2+ homeostasis. These data, taken together, demonstrate that gp120 induces apoptosis in cortical neurons, an effect that can be related to the impairment of Ca2+ homeostasis, and that TGF-beta1 pretreatment reverts both the neuronal death and the alterations in neuronal [Ca2+]i.
Scorziello
A
A
Institute of Pharmacology, School of Medicine, University of Genova, Italy.
Florio
T
T
Bajetto
A
A
Thellung
S
S
Schettini
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology; D016257:Fura-2; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016207:Cytokines; D015699:HIV Envelope Protein gp120; D016212:Transforming Growth Factor beta; D002118:Calcium; D016257:Fura-2