J Bacteriol Virol.  2014 Mar;44(1):102-107. 10.4167/jbv.2014.44.1.102.

HIV-1 Tat Protein Promotes Amyloid beta Generation and Tau Phosphorylation in Rat Hippocampal Slices

• Lee EO
• Jhang KA
• An YW
• Ju W
• Chong YH

• KMID: 2135363
• DOI: http://doi.org/10.4167/jbv.2014.44.1.102

Abstract

HIV-1 Tat protein has been implicated as a causative agent in the pathogenesis of HIV-1-associated neurocognitive disorder (HAND) and Alzheimer's disease (AD)-like pathology in HIV-1 infected patients. Here, we provide insights into the potential roles of extracellular HIV-1 Tat protein in amyloid beta (Abeta) generation and Tau phosphorylation, two major neuropathological features of AD. Exposure of the rat hippocampal slices to the full-length HIV-1 Tat protein (Tat1-86) for 3 days led to the increased levels of Abeta precursor protein (APP) accumulation, which accompanied by Abeta generation in the hippocampus, the brain region most commonly damaged in HIV-1-associated dementia (HAD). Moreover, extracellular HIV-1 Tat significantly stimulated the level of phosphrylated Tau (pTau) identified using immunoblotting with AT8 antibody, which recognizes abnormally hyperphosphorylated Tau. Collectively, our data suggest that HIV-1 Tat plays important roles in increasing the levels of APP accumulation, Abeta generation and Tau phosphorylation in the hippocampus, and thereby might contribute to the development of AD-like pathology in HIV-1-infected patients.

Keyword

HIV-1-associated neurocognitive disorder; HIV-1 Tat; pTau; Abeta; Hippocampus; Alzheimer's disease

MeSH Terms

Alzheimer Disease
Amyloid*
Animals
Brain
Dementia
Gene Products, tat*
Hippocampus
HIV-1*
Humans
Immunoblotting
Pathology
Phosphorylation*
Rats*
Amyloid
Gene Products, tat

Figure

• 

  Figure 1. Tat1-86 increased the level of APP accumulation and Aβ1-40 generation in the hippocampus. The hippocampal slices were treated for 3 days with Tat1-86 (1 μM) or vehicle only. (A) Western blots showing the Tat-induced increase of APP accumulation in hippocampal slices. Total lysates were analyzed via immunoblotting with 22C11 antibody to identify membrane APP or soluble form of APP derivatives. The blots were stripped and developed with anti-β-actin for equal protein loading. The data represent three independent experiments. (B) A normalized densitometric quantification of APP against β-actin for equal protein loading. (C) The levels of Aβ1-40 released in the slice culture media were assessed by using a specific Aβ ELISA kit. The results of triplicate experiments are expressed as the means ± SEM. *p < 0.05 versus vehicle-treated samples.

• 

  Figure 2. Tat1-86 promoted the level of phosphorylated Tau (pTau) in hippocampal slices. The slices were treated for 3 days with Tat1-86 (1 μM) or vehicle only. (A) Western blots showing the Tat-induced increase of highly phosphorylated Tau (pTau) in hippocampal slices. Total lysates were analyzed via immunoblotting with Tau-5 antibody to recognize total Tau protein or with AT8 antibody to detect hyperphosphorylated Tau. (B) A normalized densitometric quantification of total Tau against β-actin for equal protein loading. (C) A normalized densitometric quantification of pTau against β-actin for equal protein loading. The results of triplicate experiments are expressed as the means ± SEM. *p < 0.05 versus vehicle-treated samples.

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