Eun Ok Lee; Kyoung A Jhang; Ye Won An; Woong Ju; Young Hae Chong

doi:10.4167/jbv.2014.44.1.102

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Lee, Jhang, An, Ju, and Chong: HIV-1 Tat Protein Promotes Amyloid β Generation and Tau Phosphorylation in Rat Hippocampal Slices

Communication

J Bacteriol Virol 2014;44(1):102-107.

Published online: 9 February 2014

DOI: https://doi.org/10.4167/jbv.2014.44.1.102

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

Eun Ok Lee¹, Kyoung A Jhang¹, Ye Won An¹, Woong Ju², Young Hae Chong^1,^*

¹Departments of Microbiology, School of Medicine, Ewha Medical Research Institute, Ewha Womans University, Seoul, Korea

²Department of Obstetrics and Gynecology, School of Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University, Seoul, Korea

^*Corresponding author: Young Hae Chong. Department of Microbiology, School of Medicine, Ewha Womans University, 911-1, Mok-6-dong, Yangcheonku, Seoul, 158-710, Korea. Phone: +82-2-2650-5739, Fax: +82-2-2653-8891, e-mail: younghae@ewha.ac.kr

^** This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2013-008931).

Received 28 February 20143 March 2014 Accepted 5 March 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 β (Aβ) 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 Aβ precursor protein (APP) accumulation, which accompanied by Aβ 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, Aβ generation and Tau phosphorylation in the hippocampus, and thereby might contribute to the development of AD-like pathology in HIV-1-infected patients.

Keywords: HIV-1-associated neurocognitive disorder, HIV-1 Tat, pTau, Aβ, Hippocampus, Alzheimer's disease

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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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