caa a22 4500 445882921 CHVBK 20180317145550.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10157-011-0421-5 doi (NATIONALLICENCE)springer-10.1007/s10157-011-0421-5 Cisplatin induces Sirt1 in association with histone deacetylation and increased Werner syndrome protein in the kidney [Elektronische Daten] [Yukitoshi Sakao, Akihiko Kato, Takayuki Tsuji, Hideo Yasuda, Akashi Togawa, Yoshihide Fujigaki, Tomoaki Kahyo, Mitsutoshi Setou, Akira Hishida] Background: Sirt1, a mammalian homolog of silent information regulator 2 (Sir2), is the founding member of class III histone deacetylase (HDAC). Methods: In this study, we examined whether Sirt1 is involved in the modification of acetylated histone H3, acetylated p53 and Werner syndrome protein (WRN), which is stabilized by Sirt1-mediated deacetylation, in cisplatin (CDDP)-induced acute renal failure (ARF) in rats. Results: Administration of CDDP (5mg/kg body weight) caused an increase in the Sirt1 protein level by 6h; this increase peaked at day 5 and declined until day 14. Sirt1 was induced to a greater extent in rats with severe ARF. In contrast, HDAC3 and HDAC5 were not induced within 24h after CDDP administration. The level of acetylated histone H3 in the kidney decreased early, i.e., at 6h, and was minimal at day 5, after which the level gradually increased by day 14. CDDP marginally induced acetylated p53 within 24h after administration. Increased WRN also became evident at 6h, and continued to be upregulated until day 5, accompanied by an increase in proliferating cell nuclear antigen (PCNA). Transfection of Sirt1 to human embryonic kidney 293 cells mitigated the CDDP-induced cellular damage. Conclusions: These findings collectively suggest that CDDP increases the level of Sirt1 protein in the kidneys in association with histone H3 deacetylation and increased WRN and PCNA production. The induced Sirt1 may work defensively to mitigate CDDP-induced tubular damage by inactivating core histone transcriptionally, and by repairing DNA damage. Japanese Society of Nephrology, 2011 Cisplatin nationallicence Sirt1 nationallicence Deacetylation nationallicence Histone H3 nationallicence Werner syndrome protein nationallicence Sakao Yukitoshi First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut Kato Akihiko Division of Blood Purification, Hamamatsu University School of Medicine, Shizuoka, Japan aut Tsuji Takayuki First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut Yasuda Hideo First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut Togawa Akashi First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut Fujigaki Yoshihide First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut Kahyo Tomoaki First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan aut Setou Mitsutoshi Department of Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan aut Hishida Akira First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut Clinical and Experimental Nephrology Springer Japan 15/3(2011-06-01), 363-372 1342-1751 15:3<363 2011 15 10157 https://doi.org/10.1007/s10157-011-0421-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10157-011-0421-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sakao Yukitoshi First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut NATIONALLICENCE 700 1- Kato Akihiko Division of Blood Purification, Hamamatsu University School of Medicine, Shizuoka, Japan aut NATIONALLICENCE 700 1- Tsuji Takayuki First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut NATIONALLICENCE 700 1- Yasuda Hideo First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut NATIONALLICENCE 700 1- Togawa Akashi First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut NATIONALLICENCE 700 1- Fujigaki Yoshihide First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut NATIONALLICENCE 700 1- Kahyo Tomoaki First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Setou Mitsutoshi Department of Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Hishida Akira First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan aut NATIONALLICENCE 773 0- Clinical and Experimental Nephrology Springer Japan 15/3(2011-06-01), 363-372 1342-1751 15:3<363 2011 15 10157 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer