Resveratrol and Sir2 Reverse Sleep and Memory Defects Induced by Amyloid Precursor Protein / 神经科学通报·英文版

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.

Research on progress on presbycusis based on cell apoptosis / 中国医学装备

Several proteins associated with apoptosis were analyzed to investigate the progress of presbycusis based on cell apoptosis. Four proteins of caspase-3, XIAP, Sir2 T1 and cytochrome C which were associated with apoptosis were selected. Influence and progress of four proteins on presbycusis were analyzed. Apoptosis is the key factor which causes presbycusis, including apoptosis of cochlear hair cells, cochlear spiral ganglion cells and primary auditory cortical neuron. There is a close relationship between the four proteins and apoptosis of hearing related cells. These four kinds of protein factors played a role in the progress of presbycusis and are expected to serve as a target for the treatment of presbycusis.

Expression and Clinical Significance of Sir2-related Enzymes-1 in Colorectal Cancer / 中国医科大学学报

Objective To investigate the expression and clinical significance of Sir2?related enzymes?1(SIRT1)in colorectal cancer. Methods The expression of SIRT1 was evaluated by immunohistochemistry in 86 selected cases of primary Colorectal cancer and 30 samples of normal rectum tissues besided carcinoma. The relationship of the expression and clinical pathological features were analyzed. Results The positive expression rate of SIRT1 in Colorectal cancer tissue was 88.4%,and significantly higher than in normal rectum tissue besided carcinoma(P<0.001). There were no correlation between the expression of SIRT1 and sex,age and tumor diameter,and significant positive correlation between the expression of SIRT1 and TNM stage (P<0.05),lymph node metastasis(P<0.05),infiltrating depth(P<0.05),and negagtive correlation between the expression of SIRT1 and tumor differentiation(P<0.05). Conclusion The positive expression rate of SIRT1 in colorectal cancer tissue was significantly higher than in normal rectum tissue besided carcinoma and intimate correlation with tumor differentiation,TNM stage,lymph node metastasis and Infiltrat?ing depth. Conclusion SIRT1 may be an important assistance gene to diagnose and judge prognosis,and may improve diagnostic rate and auxiliari?ly judge prognosis as a important Colorectal cancer marker.

Molecular Cloning and Characterization of Two Hommologues of Yeast Sir2 Gene in the Parasitic Protist Trichomonas vaginalis / 热带医学杂志

Objective To screen cell growth and senescence-related genes of the parasitic pmtist Trichomonas vaginalis,we launched an EST program and isolated two cDNA clones from a T.vaginalis cDNA library,which showed high homology in deduced amino acid sequences to yeast Sir2 and designated as TvSir2 and TvSir2-like.Method The cDNA sequence of TvSIR2 had a length of 1034 base pairs (bp) with an open reading frame of 915 bp,and TvSIR2-like,1214 bp with an open reading frame of 1116 bp.Result The two deduced amino acid sequences shared all the three conserved cole domains with yeast Sir2 and its homologues,suggesting that the two clones were Sir2 homologues. A cDNA fragment from each cDNA clone was subvloned into the expression vector pET-41a.The expression of the fusion proteins in E.coli BL21 stains was induced by isopropylthio-β-D-galactoside (IPTG).Two anti-sera were prepared by immunizing two guinea pigs with the purified fusion proteins, Western-blot analysis demonstrated that each anti-serum reacted with the corresponding recombinant protein and detected a clear band (TvSir2,34 000 Mr;TvSir2-like,42 000 Mr)in protein extracts of the protist.Immunofluolescence techniques showed that TvSir2 and TvSir2-like proteins were both localized in the legions of perinuelear (ER) and Golgi complex.Conclusion Our data suggest that TvSir2 and TvSir2-like were two members of Sir2 family.Their biological functions in the protist would be further studied.

Construction of Prokaryotic Expression Vector for Trichomonas vaginalis Silent Information Regulator 2 and Its Expression / 中国寄生虫学与寄生虫病杂志

Total RNA was isolated from Trichomonas vaginalis and Tv-Sir2-like cDNA was amplified by RT-PCR and cloned into pGEM-T Easy plasmid. A fragment of Tv-Sir2-like cDNA was subcloned into the expression vector pET-41b and expressed in E.coli BL21 with induction of IPTG. The full-length of Tv-Sir2-like cDNA was cloned and sequenced. The prokaryotic expression system of pET-41b/Tv-Sir2-like was constructed. The fusion protein of Tv-Sir2-like was expressed in E.coli BL21, occupying 30% of the total bacterial protein after being induced by IPTG for 5 h. SDS-PAGE analysis showed that the fusion protein was about Mr 59 000. The recombinant protein of Tv-Sir2-like is efficiently expressed in E.coli BL21.