ABSTRACT
Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with diverse physiological functions. A variety of small molecules have been developed to interrogate the physiological function of SIRTs. Therefore, it is desirable to establish efficient and convenient assays to screen SIRTs modulators. In this study, we designed a series of fluorescent nonapeptide probes derived from substrates of SIRT1-SIRT3. Fluorescence increment of these probes is based on SIRT-mediated removal of the acyl side chain with fluorophore, which makes this system free of lysine-recognizing protease. Comparing the reaction of these fluorescent nonapeptide substrates with SIRT1-SIRT3 and SIRT6, it was confirmed that this assessment system was the most suitable for SIRT2 activity detection. Thus, SIRT2 was used to modify substrates by truncating the amino acids or lysine side chain of nonapeptide. Finally, two specific and efficient fluorescent probes for SIRT2, ne-D9 and ne-K4a, were developed. Evaluation of the results revealed that ne-K4a based assay was more suitable for modulators screening , while the other specific substrate ne-D9 was stable in cell lysate and could detect the activity of SIRT2 in the same. In summary, this study presents a novel strategy for detecting SIRT2 activity and in cell lysate.
ABSTRACT
Cellular autophagy is a major degradative pathway for clearance of aggregate-prone proteins and damaged organelles. It plays an important role in regulating cellular homeostasis, cell growth and development, and disease development. Dysfunctional autophagy contributes to the pathology of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, in which specific pathological protein accumulation occurs. A growing body of evidence suggests that resveratrol plays a significantly role in the regulation of autophagy and clearance of pathological proteins. Resveratrol is a potential drug for neurodegenerative diseases therapy. This review focuses on the effects of resveratrol on cellular autophagy and clinical application in the control of neurodegenerative diseases.
ABSTRACT
FoxO as an important transcription factors,can be deacetylated by SIRT1 (a sort of deacetylases),SIRT1-FoxO-au-tophagy pathway is likely to play a vital role in some diseases,e. g.diabetes,aging,obesity,cancer,cardiovascular diseases and muscle atrophy,etcetera.This paper aims to analy transcription-al regulation mechanism of FoxO,and reviews the progress of SIRT1-FoxO-autophagy pathway.
ABSTRACT
OBJECTIVE: To study the chemical constituents of Sargassum thunbergii. METHODS: The compounds were isolated and purified upon extensive column chromatography using silica gel, ODS, Sephadex LH-20, and prepative HPLC, while their structures were identified on the basis of physicochemical properties and spectroscopic data analysis. RESULTS: Fifteen compounds were isolated from the EtOH extract. The structures were identified as(+)-isololiolide(1), (-)-loliolide(2), loliolide acetate(3) grasshopper ketone(4), apo-9β-fucoxanthinone(5), 3α-hydroxy-5, 6-epoxy-7-megastigmen-9-one(6), deacetylate-apo-13'-fucoxanthinone(7), apo-13'-fucoxanthinone(8),(R)-(-)-3-hydroxy-β-ionone(9) and 6 other compounds sargassum ketone(10), 2-heptenoicacid, 4,4-dihydroxy-2,3-dimethyl-7-lactone(11), (R)-2-hydroxy-3-phenylpropanamide(12), thymidine(13), fucosterol(14) and hexade-canoic acid-2β, 3β-dihydroxypropyl ester(15). CONCLUSION: Deacetylate-apo-13'-fucoxanthinone is a new compound, and compounds 3,5,6,8,9,15 are obtained from the genus Sargassum for the first time.