Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes
Open accessAbstract
Histone deacetylase 6 (HDAC6) likely is important in inflammatory diseases. However, how HDAC6 exerts its effect on inflammatory processes remains unclear. HIV-1 transactivator of transcription (Tat) activates NADPH oxidase resulting in generation of reactive oxygen species (ROS), leading to extensive neuro-inflammation in the central nervous system. We investigated the correlation of HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6 knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N-acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10. Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent expression of chemokines. The collective results point to the potential crosstalk between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for relief of HIV-1 Tat-mediated neuro-inflammation.
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HDAC6 knockdown attenuates ROS generation, NADPH oxidase activation, and neuroinflammation response in HIV-1 Tat-stimulated astrocytes.
“HDAC6 knockdown attenuates reactive oxygen species (ROS) generation, NADPH oxidase activation, and neuroinflammation response in HIV-1 transactivator of transcription (Tat)-stimulated astrocytes [184].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [184]
Nox2 knockdown suppresses HIV-1 Tat-induced HDAC6 expression and subsequent upregulation of pro-inflammatory chemokines.
“In addition, Nox2 knockdown suppresses HIV-1 Tat-induced HDAC6 expression and subsequent upregulation of pro-inflammatory chemokines [184], indicating a possible link between neuroinflammation and mediation of HDAC6.”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [184]
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Cites
HDAC6 is a microtubule-associated deacetylase
Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X.-F., & Yao, T.-P. (2002) · Nature · doi:10.1038/417455a · Cited by 2,403 · see citing works
NF-κB activation by reactive oxygen species: Fifteen years later
Gloire, G., Legrand-Poels, S., & Piette, J. G. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.04.011 · Cited by 1,540 · see citing works
Nox proteins in signal transduction
Brown, D. I., & Griendling, K. (2009) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2009.07.023 · Cited by 841 · see citing works
Nox family NADPH oxidases: Molecular mechanisms of activation.
Brandes, R., Weissmann, N., & Schröder, K. (2014) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2014.07.046 · Cited by 660 · see citing works
Regulation of Nox and Duox enzymatic activity and expression
Lambeth, J. D., Kawahara, T., & Diebold, B. A. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.03.028 · Cited by 498 · see citing works
Aldana-Masangkay, G. I., & Sakamoto, K. M. (2010) · BioMed Research International · doi:10.1155/2011/875824 · Cited by 375 · see citing works
Differential activation of astrocytes by innate and adaptive immune stimuli
Carpentier, P. A., Begolka, W. S., Olson, J. K., Elhofy, A., Karpus, W. J., & Miller, S. D. (2004) · Glia · doi:10.1002/glia.20117 · Cited by 359 · see citing works
Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes
Li, Y., Shin, D., & Kwon, S. H. (2012) · FEBS Journal · doi:10.1111/febs.12079 · Cited by 346 · see citing works
New Insights on <i>NOX</i> Enzymes in the Central Nervous System
Nayernia, Z., Jaquet, V., & Krause, K.-H. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5703 · Cited by 279 · see citing works
Expression and Modulation of an NADPH Oxidase in Mammalian Astrocytes
Abramov, A. Y., Jacobson, J., Wientjes, F. B., Hothersall, J. S., Canevari, L., & Duchen, M. R. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1632-05.2005 · Cited by 228 · see citing works
Kutsch, O., Oh, J., Nath, A., & Benveniste, E. N. (2000) · Journal of Virology · doi:10.1128/jvi.74.19.9214-9221.2000 · Cited by 178 · see citing works
Molecular pathway involved in HIV-1-induced CNS pathology: role of viral regulatory protein, Tat
Rappaport, J., Joseph, J., Croul, S. E., et al. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.65.4.458 · Cited by 171 · see citing works
Two Catalytic Domains Are Required for Protein Deacetylation
Zhang, Y., Gilquin, B., Khochbin, S., & Matthias, P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500241200 · Cited by 161 · see citing works
Role of the Tetradecapeptide Repeat Domain of Human Histone Deacetylase 6 in Cytoplasmic Retention
Bertos, N., Gilquin, B., Chan, G. K. T., Yen, T. J., Khochbin, S., & Yang, X. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408583200 · Cited by 160 · see citing works
Youn, G. S., Lee, K., Choi, S. Y., & Park, J. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.05.014 · Cited by 152 · see citing works
Self-citationDevelopment and therapeutic impact of HDAC6-selective inhibitors
Dallavalle, S., Pisano, C., & Zunino, F. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.06.014 · Cited by 137 · see citing works
Specific Interaction of the Human Immunodeficiency Virus Tat Proteins with a Cellular Protein Kinase
Herrmann, C. H., & Rice, A. P. (1993) · Virology · doi:10.1006/viro.1993.1634 · Cited by 134 · see citing works
Roles and functions of HIV-1 Tat protein in the CNS: an overview
Bagashev, A., & Sawaya, B. E. (2013) · Virology Journal · doi:10.1186/1743-422x-10-358 · Cited by 131 · see citing works
Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production
Wang, B., Rao, Y.-H., Inoue, M., Hao, R., Lai, C.-H., Chen, D. J., McDonald, S. L., Choi, M.-C., Wang, Q., Shinohara, M. L., et al. (2014) · Nature Communications · doi:10.1038/ncomms4479 · Cited by 127 · see citing works
Vishwakarma, S., Iyer, L. R., Muley, M. M., Singh, P., Shastry, A., Saxena, A., Kulathingal, J., Vijaykanth, G., Raghul, J., Rajesh, N., et al. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.03.016 · Cited by 124 · see citing works
Zhang, L., Pang, S., Deng, B., Qian, L., Chen, J., Zou, J., Zheng, J., Linghui, Y., Zhang, C., Chen, X., et al. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.01.001 · Cited by 123 · see citing works
HDAC6 regulates cellular viral RNA sensing by deacetylation of RIG‐I
Choi, S. J., Lee, H., Kim, J., Park, S. Y., Kim, T., Lee, W., Jang, D., Yoon, J., Choi, Y., Kim, S., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201592586 · Cited by 119 · see citing works
Self-citationPKC alpha regulates Sendai virus‐mediated interferon induction through HDAC6 and β‐catenin
Zhu, J., Coyne, C. B., & Sarkar, S. N. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.351 · Cited by 103 · see citing works
HIV-TAT Protein Upregulates Expression of Multidrug Resistance Protein 1 in the Blood–Brain Barrier
Hayashi, K., Pu, H., Andras, I. E., Eum, S. Y., Yamauchi, A., Hennig, B., & Toborek, M. J. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600254 · Cited by 94 · see citing works
Turchan-Cholewo, J. T., Smith, V. D., Gupta, S., Gorospe, R. M. C., Keller, J. N., & Bruce‐Keller, A. J. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2097 · Cited by 76 · see citing works
Human immunodeficiency virus type 1 TAT protein induces adhesion molecule expression in astrocytes
Woodman, S. E., Benveniste, E. N., Nath, A., & Berman, J. W. (1999) · Journal of NeuroVirology · doi:10.3109/13550289909021296 · Cited by 66 · see citing works
Chattopadhyay, S., Fensterl, V., Zhang, Y., et al. (2013) · mBio · doi:10.1128/mbio.00636-12 · Cited by 66 · see citing works
HIV-1 Tat Activates Dual Nox Pathways Leading to Independent Activation of ERK and JNK MAP Kinases
Wu, R. F., Ma, Z., Myers, D. P., & Terada, L. S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704481200 · Cited by 65 · see citing works
Molecular mechanisms of HIV-1 associated neurodegeneration
Özdener, M. H. (2005) · Journal of Biosciences · doi:10.1007/bf02703676 · Cited by 64 · see citing works
HDAC6 Deacetylase Activity Is Critical for Lipopolysaccharide-Induced Activation of Macrophages
Yan, B., Xie, S., Liu, Z., Ran, J., Li, Y., Wang, J., Yang, Y., Zhou, J., Li, D., & Liu, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110718 · Cited by 61 · see citing works
Developments in HIV Neuropathogenesis
Nath, A., & Rumbaugh, J. A. (2006) · Current Pharmaceutical Design · doi:10.2174/138161206776055877 · Cited by 56 · see citing works
Kim, S., Lee, J., Cho, W., Cho, K., Sakong, J., Kim, J., Chin, B., & Baek, S. (2009) · Immunology and Cell Biology · doi:10.1038/icb.2009.87 · Cited by 56 · see citing works
Molecular Mechanisms of Neurodegenerative Diseases Induced by Human Retroviruses: A Review
Irish (2009) · American Journal of Infectious Diseases · doi:10.3844/ajidsp.2009.231.258 · Cited by 55 · see citing works
Song, H. Y., Ryu, J., Ju, S. M., et al. (2007) · Experimental & Molecular Medicine · doi:10.1038/emm.2007.4 · Cited by 54 · see citing works
Cooperative induction of CXCL10 involves NADPH oxidase: Implications for HIV dementia
Williams, R., Yao, H., Peng, F., et al. (2009) · Glia · doi:10.1002/glia.20949 · Cited by 53 · see citing works
HIV ‐1 Tat C modulates NOX 2 and NOX 4 expressions through miR‐17 in a human microglial cell line
Jadhav, V., Krause, K., & Singh, S. K. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12933 · Cited by 51 · see citing works
Bethel-Brown, C. S., Yao, H., Callen, S. E., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002235 · Cited by 50 · see citing works
Youn, G. S., Ju, S. M., Choi, S. Y., & Park, J. (2015) · Glia · doi:10.1002/glia.22865 · Cited by 49 · see citing works
Self-citationNam, H. J., Kang, J. K., Kim, S.-K., Ahn, K. J., Seok, H., Park, S. J., Chang, J., Pothoulakis, C., LaMont, J. T., & Kim, H. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.162743 · Cited by 49 · see citing works
Rhim, H., Echetebu, C. O., Herrmann, C. H., et al. (1994) · PubMed · Cited by 45 · see citing works
Song, H. Y., Ju, S. M., Seo, W. Y., et al. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.12.019 · Cited by 42 · see citing works
Gorina, R., Sanfeliu, C., Galitó, A., Messeguer, Á., & Planas, A. M. (2007) · Glia · doi:10.1002/glia.20542 · Cited by 41 · see citing works
Deng, B., Xie, S., Wang, J., Xia, Z., & Nie, R. (2012) · Journal of Vascular Research · doi:10.1159/000332337 · Cited by 39 · see citing works
HIV Neuropathogenesis: a Tight Rope Walk of Innate Immunity
Yao, H., Bethel-Brown, C. S., Li, C. Z., & Buch, S. J. (2010) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-010-9211-1 · Cited by 33 · see citing works
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- [44]Brown D.I. Griendling K.K. Nox proteins in signal transduction Free Radic. Biol. Med. 47 2009 1239 1253 19628035 PMC2763943
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Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
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“HDAC6 knockdown attenuates reactive oxygen species (ROS) generation, NADPH oxidase activation, and neuroinflammation response in HIV-1 transactivator of transcription (Tat)-stimulated astrocytes [184].”
Background
- Authors
- Youn, G. S., Cho, H., Kim, D., Choi, S. Y., & Park, J.
- Affiliations
- Hallym University (KR)
- Corresponding author
- Park, Jinseu
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 12
- Pages
- 978-986
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC5429231
- OpenAlex
- W2611766569
- Cited by
- 44
- References
- 44
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 1
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ministry of Education (HRF-201607-010)
- National Research Foundation of Korea
- Hallym University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- HDAC6, NADPH oxidase, NOX2, HIV-1 Tat protein, astrocytes, reactive oxygen species, neuroinflammation, chemokines, MCP-1, interleukin-8, CXCL10, tubastatin A, p47phox, p22phox, histone deacetylase
- MeSH terms
- Histone Deacetylase 6, NADPH Oxidase 2, Animals, Astrocytes, Cell Line, Humans, Hydroxamic Acids, Indoles, HIV-1, Reactive Oxygen Species, Chemokines, Mice, tat Gene Products, Human Immunodeficiency Virus, Gene Knockdown Techniques
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