- 作者: Vivian Hawkins Qian Shen Chuang chin Chiueh
- 作者服務機構: Howard Huges Medical Institute Student Teacher Internship Program, Montgomery County Public School, and National Institutes of Health; Unit on Neurodegeneration and Neuroprotection, Laboratory of Clinical Science, National Institute of Medntal Health, National Institutes Of Health, bethesda, Md., USA
- 中文摘要: --
- 英文摘要: A significant number of adult male patients with ac-quired immunodeficiency syndrome develop cerebralatrophy and progressive brain disorders such as demen-tia complex and neuropsychiatric problems. Upon enter-ing the brain via activated macrophages or microglias,the human immunodeficiency type 1 virus (HIV-1) mayproduce cytotoxic factors such as HIV-1 envelope protein(gp120) and protease. Owing to significant proteolysis ofnonviral proteins, the protease derived from HIV-1 maybe detrimental to brain cells and neurons. Our resultsrevealed that HIV-1 protease, at nanomolar concentra-tions, was as potent as gp120 in causing neurotoxicity inhuman neuroblastoma neurotypic SH-SY5Y cells. Asshown by the Oncor ApopTag staining procedure, HIV-1protease significantly increased the number of apoptoticcells over the serum-free controls. Moreover, HIV-1 pro-tease-induced neurotoxicity was blocked by a selectiveprotease inhibitor, kynostatin (KNI-272). Antioxidantssuch as 17β-estradiol, melatonin, and S-nitrosogluta-thione also prevented protease-induced neurotoxicity.These findings indicate that oxidative proteolysis maymediate HIV-1 protease-induced apoptosis and the de-generation of neurons and other brain cells. Centrallyactive protease inhibitors and antioxidants may play animportant role in preventing cerebral atrophy and associ-ated dementia complex caused by HIV-1.
- 中文關鍵字: --
- 英文關鍵字: AIDS dementia complex. Antioxidants. Apoptosis Cerebral atrophy. gp120. HIV-1 protease. Human neuroblastoma cell. Neurprotection. Protease inhibitor(KNI-272)