{"title":"Natural Polyphenols Inhibit Lysine-Specific Demethylase-1 <i>in vitro.</i>","authors":"Arian Abdulla, Xiaoping Zhao, Fajun Yang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Natural polyphenols, such as resveratrol, have beneficial functions on major human diseases such as cancer, diabetes, and cardiovascular disease. Besides acting as antioxidants, some of these polyphenols can also target proteins to modulate specific biological pathways. The lysine-specific histone demethylase LSD1 plays important roles in cell growth, differentiation and nutrient metabolism. Here, we studied the effect of natural polyphenols resveratrol, curcumin, quercetin and analogs on LSD1. Using <i>in vitro</i> LSD1 enzymatic assays, we show that resveratrol, curcumin and quercetin displayed a potent inhibitory effect on the LSD1 activity and were more potent than the known LSD1 inhibitor trans-2-phenylcyclopropylamine (TCP). The new function of resveratrol, curcumin and quercetin is independent of their antioxidant properties, as other antioxidants had no effect on LSD1 under the similar conditions. In C2C12 fibroblasts, resveratrol and curcumin can efficiently inhibit myogenic expression and differentiation, for which LSD1 is required. Thus, our study has identified LSD1 as a novel target of bioactive natural compounds, such as resveratrol, curcumin and quercetin, and such finding suggests that LSD1 inhibition can at least partially contribute to some of the previously observed beneficial effects of these compounds.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 1","pages":"56-63"},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646376/pdf/nihms465947.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31420132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liang-Jun Yan, Nopporn Thangthaeng, Nathalie Sumien, Michael J Forster
{"title":"Serum Dihydrolipoamide Dehydrogenase Is a Labile Enzyme.","authors":"Liang-Jun Yan, Nopporn Thangthaeng, Nathalie Sumien, Michael J Forster","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Dihydrolipoamide dehydrogenase (DLDH) is a multifunctional oxidoreductase and is well known as an essential component of four mammalian mitochondrial multienzyme complexes: pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched chain α-keto acid dehydrogenase, and the glycine cleavage system. However, existence of extracellular DLDH in mammals, if any, has not been clearly defined. The present article reports identification and biochemical characterization of serum DLDH. Proteomic analysis of rat serum using blue native polyacrylamide gel electrophoresis (BN-PAGE) and mass spectrometry peptide sequencing led to generation of 6 tryptic peptides in one band that matched to mitochondrial DLDH, indicating the existence of DLDH in rat serum. Measurement of enzymatic activity also indicated the existence of DLDH in human and mouse serum. Further biochemical analysis of rat serum DLDH revealed that this enzyme lacked diaphorase activity and could not be detected on Western blots probed with antibodies that recognized mitochondrial DLDH. Moreover, both ammonium sulfate fractioning and gel filtration of serum samples rendered a great loss in DLDH activity, indicating that the enzyme activity of this serum protein, unlike that of mitochondrial DLDH, is very labile. When DTT was supplemented in the buffer used for gel filtration, DLDH activity was found to be largely preserved; indicating that serum DLDH is susceptible to air-implicated inactivation. Results of the present study indicate that serum DLDH differs from mitochondrial DLDH in that it is a very labile enzyme.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 1","pages":"30-42"},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641859/pdf/nihms449718.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31408605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protein Oxidative Modifications: Beneficial Roles in Disease and Health.","authors":"Zhiyou Cai, Liang-Jun Yan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Protein oxidative modifications, also known as protein oxidation, are a major class of protein posttranslational modifications. They are caused by reactions between protein amino acid residues and reactive oxygen species (ROS) or reactive nitrogen species (RNS) and can be classified into two categories: irreversible modifications and reversible modifications. Protein oxidation has been often associated with functional decline of the target proteins, which are thought to contribute to normal aging and age-related pathogenesis. However, it has now been recognized that protein oxidative modifications can also play beneficial roles in disease and health. This review summarizes and highlights certain positive roles of protein oxidative modifications that have been documented in the literature. Covered oxidatively modified protein adducts include carbonylation, 3-nitrotyrosine, s-sulfenation, s-nitrosylation, s-glutathionylation, and disulfide formation. All of which have been widely analyzed in numerous experimental systems associated with redox stress conditions. The authors believe that selected protein targets, when modified in a reversible manner in prophylactic approaches such as preconditioning or ischemic tolerance, may provide potential promise in maintaining health and fighting disease.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 1","pages":"15-26"},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646577/pdf/nihms-445524.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31420134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms of Lower Urinary Tract Symptoms in Pelvic Ischemia.","authors":"Kazem M Azadzoi, Mike B Siroky","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The etiology of lower urinary tract symptoms is poorly understood. The pathophysiology of detrusor instability, voiding dysfunction and pelvic pain in patients with non-obstructed bladder remains highly controversial. In the male, most cases of lower urinary tract symptoms are attributed to bladder outlet obstruction due to benign prostatic hyperplasia. However, urodynamic data have revealed that in approximately one third to more than one half of cases, lower urinary tract symptoms are not associated with enlarged prostate or bladder outlet obstruction. Interestingly, lower urinary tract symptoms questionnaires in women yield scores that are similar to their age-matched male counterparts. These observations imply that aging-associated sex-independent changes in bladder vasculature, nerves, smooth muscle and epithelium may play a role in the development of lower urinary tract symptoms. Epidemiologic studies have shown a close correlation between vascular occlusive disorders and the prevalence of lower urinary tract symptoms. International prostate symptom scores were found to be significantly worse in men with cardiovascular disorders than symptomatic patients without cardiovascular problems. Clinical trials have revealed a close correlation between decreased pelvic blood flow and severity of lower urinary tract symptoms in the elderly patients. Studies with experimental models of pelvic ischemia have shown that accumulation of reactive oxygen species in the ischemic bladder initiates a cascade of cellular, subcellular and molecular reactions. These reactions to ischemia appear to compromise bladder structure and function leading to neurodegeneration, smooth muscle instability, increased contractile activity, fibrosis and non-compliance. These observations collectively introduce a new concept in the pathophysiology of voiding dysfunction suggesting that pelvic ischemia may be an independent factor in the development of non-obstructed non-neurogenic overactive bladder and lower urinary tract symptoms.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 1","pages":"64-74"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547274/pdf/nihms-1700271.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39570457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}