RESUMO
Histone lysine methylation contributes to transcriptional regulation by serving as a platform for the recruitment of various cofactors. Intense studies have been conducted for elucidating the functional meaning of H3K79 methylation, and to date, the only known HMTase responsible for the modification was DOT1L. In this study, we report that the MMSET isoform RE-IIBP has HMTase activity for H3K79. It was uncovered that RE-IIBP up-regulates MEIS1 transcription through H3K79 methylation via recruitment to the MEIS1 promoter. By means of proteomic and biochemical analysis, association of RE-IIBP with the E3 ubiquitin ligase RNF20 was demonstrated for synergistic activation of MEIS1 transcription via H3K79 HMTase activity. Furthermore, It was observed that RE-IIBP induces MEIS1-mediated apoptosis, which was dependent on H2BK120 ubiquitination by RNF20. These findings suggest RE-IIBP as another candidate for further studies to elucidate the mechanism of H3K79 methylation and its biological functions.
Assuntos
Apoptose/fisiologia , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Repressoras/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/fisiologia , Linhagem Celular , Histona-Lisina N-Metiltransferase/genética , Histonas/genética , Proteínas de Homeodomínio/genética , Humanos , Metilação , Proteína Meis1 , Proteínas de Neoplasias/genética , Proteínas Repressoras/genética , Transcrição Gênica/fisiologia , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: The autonomic nervous system plays a central role in the maintenance of hemodynamic stability. Cardiac autonomic dysfunction may result in serious complications, such as sudden cardiac death. Heart rate variability (HRV) is significantly reduced in patients undergoing chronic hemodialysis (HD). The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on the autonomic nervous system in chronic HD patients. METHODS: Forty chronic HD patients were prospectively studied. The participants were divided into conventional HD and OL-HDF groups. They received regular high-flux HD or OL-HDF for 4-hour sessions, three times a week. Time-and frequency-domain measures of the 24-hour HRV were analyzed during the interdialytic period prior to postdilution OL-HDF and every 6 months for 24 months. The 7-year survival was also evaluated. RESULTS: Among the 40 participants, 15 patients in the HD group and 11 patients in the OL-HDF group completed the study. There was no difference in the baseline characteristics. After 24 months of treatment, ß2-microglobulin concentration decreased (from 33.4±15.2 mg/dL to 28.4±6.2 mg/dL, P =0.02) in the OL-HDF group, while there was no change in the HD group. In the HRV analysis, the frequency-domain HRV parameters increased significantly compared with baseline in the OL-HDF group [natural logarithmic high frequency (lnHF), 3.15±3.36 ms(2) vs. 4.42±3.81 ms(2); ln low frequency (LF), 3.56±3.17 ms(2) vs. 4.78±3.99 ms(2); ln very low frequency (VLF), 4.90±4.62 ms(2) vs. 6.38±5.54 ms(2); LF/HF ratio, 1.4±0.4 vs. 2.5±0.1]. The survival rate was similar between the groups. CONCLUSION: This study shows that OL-HDF improved autonomic nervous system dysfunction in chronic HD patients.
RESUMO
CONCLUSION: Human beta-defensin-1 (hBD-1) and human beta-defensin-2 (hBD-2) antimicrobial peptides present in the cerumen, which is composed of exfoliated epithelial keratin and gland secretion, might provide the first line of defense against microbes in external auditory canal (EAC) skin. OBJECTIVES: Cerumen (earwax) plays a primary role in protecting the EAC skin and tympanic membrane. Even though the protection by antimicrobial peptides present in the skin secretion has been well established, little is known about the intrinsic role of the peptides in the EAC skin and cerumen. The aim of this study was to examine the presence of important antimicrobial peptides, hBD-1 and hBD-2, in the cerumen and EAC skin. MATERIALS AND METHODS: Cerumen was collected from 20 healthy adults, and the EAC skins were obtained from 12 patients who underwent middle ear surgery with canaloplasty. The presence of hBD-1 and hBD-2 was analyzed using immunohistochemistry and Western blotting. RESULTS: In the immunohistochemical study of the EAC skin, expression of hBD-1 and hBD-2 was observed in both the epithelium and the glands. The presence of hBD-1 and hBD-2 peptides in the cerumen was confirmed by Western blotting.
