Growth hormone prevents human immunodeficiency virus-induced neuronal p53 expression.
Growth hormone (GH) is neuroprotective, presumably through its actions on GH receptor-mediated pathways. Here, we examined the effects of GH using in vitro and in vivo assays of human immunodeficiency virus (HIV)-induced neuronal injury. Neuronal cultures were in assays of neurotoxicity induced by supernatants from HIV-1 tat-transfected monocytoid cells (Tat supernatant). GH treatment reduced neuronal death compared with untreated cultures (p < 0.001), which was blocked by a GH receptor antagonist, B2036. Tat supernatant-induced p53 expression in neurons was also reduced by GH treatment. Expression of both p53 and GH receptor were increased in brain tissue from HIV-infected persons compared with controls (p < 0.05). Mice receiving intrastriatal implants of Tat supernatant and treated with GH showed less neurobehavioral abnormalities together with reduced neuroinflammation and neuronal injury compared with untreated animals (p < 0.01). Three acquired immunodeficiency syndrome-defined patients with neurocognitive impairment were serially evaluated during daily GH treatment showing a sustained improvement in neuropsychological performance (p < 0.01). GH prevents neuronal death through its actions on neurons involving a p53-mediated pathway and also improved in vivo neurological function, indicating that GH may have a role in the treatment of HIV-induced neurodegeneration.
Silva
Claudia
C
Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
Zhang
Kunyan
K
Tsutsui
Shigeki
S
Holden
Janet K
JK
Gill
M John
MJ
Power
Christopher
C
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D017077:Culture Media, Conditioned; D015696:Gene Products, tat / Q000235:genetics*; D013006:Growth Hormone / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009483:Neuropsychological Tests; D011986:Receptors, Somatotropin / Q000378:metabolism; D020079:Terminal Repeat Sequences; D014162:Transfection; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D020298:U937 Cells; D054322:tat Gene Products, Human Immunodeficiency Virus
D017077:Culture Media, Conditioned; D015696:Gene Products, tat; D011986:Receptors, Somatotropin; D016159:Tumor Suppressor Protein p53; D054322:tat Gene Products, Human Immunodeficiency Virus; D013006:Growth Hormone