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Selective inhibitor of histone deacetylase 6 (tubastatin A) suppresses proliferation of hepatitis C virus replicon in culture of human hepatocytes

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Abstract

Acetylation of α-tubulin was studied in cultures of human hepatocytes under the influence of selective inhibitors of histone deacetylases HDAC6 and SIRT-2 — tubastatin A and 2-(3-phenethoxyphenylamino)benzamide, respectively. It was found that in hepatocyte cell line HepG2 acetylated α-tubulin is accumulated preferentially on inhibition of HDAC6 but not of SIRT-2. Under the same conditions, no acetylation of α-tubulin was observed in hepatocyte cell line Huh7. However, the inhibition of HDAC6 with tubastatin A led to hyperacetylation of α-tubulin and simultaneously to decrease in viral RNA concentration in hepatocyte cell line Huh7-luc/neo, which supports propagation of the full genome replicon of hepatitis C virus. The correlation between these two processes points to HDAC6 as a promising cellular target for therapy of hepatitis C.

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Abbreviations

HCV:

hepatitis C virus

HDAC6:

Zn2+-dependent histone deacetylase 6

MT:

microtubules

SIRT-2:

NAD+-dependent histone deacetylase

αTAT1:

α-tubulin acetyltransferase of mammals

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991, Moscow, Russia

    M. V. Kozlov, A. A. Kleymenova, K. A. Konduktorov & S. N. Kochetkov

  2. Kazan Federal University, ul. Kremlyovskaya 18, 420008, Kazan, Republic of Tatarstan, Russia

    A. Z. Malikova

Authors
  1. M. V. Kozlov
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  2. A. A. Kleymenova
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  3. K. A. Konduktorov
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  4. A. Z. Malikova
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  5. S. N. Kochetkov
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Correspondence to M. V. Kozlov.

Additional information

Original Russian Text © M. V. Kozlov, A. A. Kleymenova, K. A. Konduktorov, A. Z. Malikova, S. N. Kochetkov, 2014, published in Biokhimiya, 2014, Vol. 79, No. 7, pp. 802–808.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM14-067, May 25, 2014.

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Kozlov, M.V., Kleymenova, A.A., Konduktorov, K.A. et al. Selective inhibitor of histone deacetylase 6 (tubastatin A) suppresses proliferation of hepatitis C virus replicon in culture of human hepatocytes. Biochemistry Moscow 79, 637–642 (2014). https://doi.org/10.1134/S0006297914070050

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  • DOI: https://doi.org/10.1134/S0006297914070050

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