著者

Shiho Nagata Tetsuro Marunouchi Kouichi Tanonaka

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b18-00785, (Released:2019-01-10)

参考文献数

38

被引用文献数

16

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Protein quality control (PQC) in the heart plays an important role to maintain cellular protein homeostasis. Impairment of PQC may cause the development of heart failure. It is well known that histone deacetylase 6 (HDAC6) is an essential enzyme for regulating the cellular PQC response. In this study, we aimed at examining the association between HDAC6 and the chaperone system and the effects of HDAC6 inhibition in the development of heart failure following myocardial infarction (MI). MI was induced by coronary artery ligation. Coronary artery-ligated and sham-operated rats were divided into groups that were orally administered suberoylanilide hydroxamic acid (SAHA) or vehicle from the 2nd to 8th week after the operation. The cardiac function and protein expression levels in the viable left ventricle were analyzed by echocardiography, western blotting, and immunohistochemistry at the 2nd and 8th weeks after the operation. The deacetylase activity of HDAC6 was markedly elevated during the development of heart failure after MI. In the failing heart, a decrease in heat-shock protein (HSP) contents and an accumulation of ubiquitinated proteins were observed, indicating PQC dysfunction. Inhibition of HDAC6 activity by SAHA treatment enhanced the translocation of heat-shock transcription factor 1 to the nucleus and induced the expression of HSP, resulting in maintenance of cellular protein homeostasis. The cardiac pump function after MI was also improved by SAHA administration. Our findings suggest that inhibition of HDAC6 activity is a novel approach for the treatment of heart failure following MI.

著者

Emi Takashita Hiroko Morita Shiho Nagata Masayuki Shirakura Seiichiro Fujisaki Hideka Miura Ikuyo Takayama Tomoko Arita Yasushi Suzuki Masaoki Yamaoka Taichiro Tanikawa Ryota Tsunekuni Junki Mine Saki Sakuma Yuko Uchida Akihiro Shibata Mari Iwanaka Noriko Kishida Kazuya Nakamura Tsutomu Kageyama Shinji Watanabe Hideki Hasegawa The Influenza Virus Surveillance Group of Japan

出版者

National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

雑誌

Japanese Journal of Infectious Diseases (ISSN:13446304)

巻号頁・発行日

pp.JJID.2021.751, (Released:2021-12-28)

参考文献数

15

被引用文献数

1

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Circulation of avian influenza A viruses in poultry is a public health concern because these viruses may cause severe disease in humans and have the potential to become more transmissible among humans. Monitoring the susceptibility of these viruses to antivirals is important for influenza pandemic preparedness. However, information about their antiviral susceptibility is limited. Here, we determined the susceptibilities of avian influenza A(H5N1), A(H5N2), A(H5N8), A(H7N7), A(H7N9), A(H9N1), and A(H9N2) viruses isolated in Japan to the antivirals approved for use there: the M2 inhibitor amantadine; the neuraminidase inhibitors oseltamivir, peramivir, zanamivir, and laninamivir; and the RNA polymerase inhibitors baloxavir and favipiravir. Genotypic methods that detect amino acid substitutions associated with antiviral resistance and phenotypic methods that assess viral susceptibility to drugs revealed that these avian influenza A viruses are susceptible to neuraminidase inhibitors and RNA polymerase inhibitors. These results suggest that the neuraminidase inhibitors and the RNA polymerase inhibitors currently approved in Japan could be a treatment option against influenza A virus infections in humans.