Neuronal glycolytic pathway impairment induced by HIV envelope glycoprotein gp120.
Neurological impairment is a common feature of Acquired Immunodeficiency Syndrome (AIDS); functional alterations have been reported both in central and peripheral nervous system and the Human Immunodeficiency Virus (HIV) envelope glycoprotein gp120 has been proposed as a neurotoxin acting through a calcium-dependent mechanism. On the other hand it has been reported that gp120 treatment also induce about a 20% decrease in the cerebral glucose utilization and in the cellular ATP levels. The reported observations were performed on experimental system where also non-neuronal cells where present; in order to evaluate whether a direct interaction between HIV proteins and neuronal cells takes place, we used a neuroblastoma cultures where only neuronal cells are present. We analysed the effects of gp120 on the N18TG2 neuroblastoma clone. Treatments were performed both on growing and confluent cultures. Short time treatment with gp120 of confluent cultures causes a 25% reduction in the level of neuron-specific enolase, resulting in a similar decrease of oxygen consumption. Long time exposure of growing cells also causes a reduction in cell survival. Furthermore, using a membrane-specific fluorescent probe we observed that gp120 produces an increase of membrane trafficking. These observations suggest a direct interaction between the viral envelope protein and neuronal cells, which results in an alteration of glycolytic metabolism. This alteration may be related to the neurologic impairments observed in AIDS patients.
Vignoli
A L
AL
Dipartimento di Biologia Cellulare e dello Sviluppo, Università La Sapienza, Rome, Italy.
Martini
I
I
Haglid
K G
KG
Silvestroni
L
L
Augusti-Tocco
G
G
Biagioni
S
S
D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D005456:Fluorescent Dyes / Q000494:pharmacology; D005699:Galactosylceramides / Q000378:metabolism; D006019:Glycolysis; D015699:HIV Envelope Protein gp120 / Q000378:metabolism* / Q000494:pharmacology*; D015151:Immunoblotting; D051379:Mice; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D005456:Fluorescent Dyes; D005699:Galactosylceramides; D015699:HIV Envelope Protein gp120; D010751:Phosphopyruvate Hydratase