The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Scott Earley - One of the best experts on this subject based on the ideXlab platform.

Chuenmao Yang - One of the best experts on this subject based on the ideXlab platform.

  • Mevastatin ameliorates sphingosine 1 phosphate induced inflammation in human tracheal smooth muscle cells
    European Respiratory Journal, 2016
    Co-Authors: Chuenmao Yang
    Abstract:

    Background: Sphingosine-1-phosphate (S1P), an important inflammatory mediator, has been shown to regulate cyclooxygenase-2 (COX-2) production and promote various cellular responses such as cell migration. Mevastatin (MVS) has been shown to effectively inhibit inflammatory responses. However, the mechanisms underlying S1P-evoked COX-2-dependent cell migration which is modulated by MVS in human tracheal smooth muscle cells (HTSMCs) remain unclear. Methods: COX-2 expression was determined by Western blotting, real time-PCR, and promoter analyses. The signaling molecules were investigated by pretreatment with respective pharmacological inhibitors or transfection with siRNAs. The interaction between COX-2 promoter and transcription factors was determined by chromatin immunoprecipitation (ChIP) assay. The effects of MVS on S1P-mediated inflammatory responses were also confirmed using animal study. Results: We observed that S1P stimulated mTOR activation through Nox2/ROS and PI3K/Akt pathways, which further stimulate FoxO1 phosphorylation and translocation to the cytosol. S1P induced CREB activation and translocation via an mTOR-independent manner. Finally, we showed that MVS markedly reduced S1P-induced cell migration and COX-2/PGE 2 production via a PPARg-dependent signaling. Conclusions: MVS attenuates the S1P-induced COX-2 expression and cell migration via the regulation of FoxO1 and CREB phosphorylation and translocation by PPARgin HTSMCs. MVS could be beneficial for prevention of airway inflammation in the future.

  • Mevastatin ameliorates sphingosine 1 phosphate induced cox 2 pge2 dependent cell migration via foxo1 and creb phosphorylation and translocation
    British Journal of Pharmacology, 2015
    Co-Authors: Chihkai Hsu, Chihchung Lin, Lider Hsiao, Chuenmao Yang
    Abstract:

    Background and Purpose Sphingosine 1-phosphate (S1P), an important inflammatory mediator, has been shown to regulate COX-2 production and promote various cellular responses such as cell migration. Mevastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA), effectively inhibits inflammatory responses. However, the mechanisms underlying S1P-evoked COX-2-dependent cell migration, which is modulated by Mevastatin in human tracheal smooth muscle cells (HTSMCs) remain unclear. Experimental Approach The expression of COX-2 was determined by Western blotting, real time-PCR and promoter analyses. The signalling molecules were investigated by pretreatment with respective pharmacological inhibitors or transfection with siRNAs. The interaction between COX-2 promoter and transcription factors was determined by chromatin immunoprecipitation assay. Finally, the effect of Mevastatin on HTSMC migration and leukocyte counts in BAL fluid and COX-2 expression induced by S1P was determined by a cell migration assay, cell counting and Western blot. Key Results S1P stimulated mTOR activation through the Nox2/ROS and PI3K/Akt pathways, which can further stimulate FoxO1 phosphorylation and translocation to the cytosol. We also found that S1P induced CREB activation and translocation via an mTOR-independent signalling pathway. Finally, we showed that pretreatment with Mevastatin markedly reduced S1P-induced cell migration and COX-2/PGE2 production via a PPARγ-dependent signalling pathway. Conclusions and Implications Mevastatin attenuates the S1P-induced increased expression of COX-2 and cell migration via the regulation of FoxO1 and CREB phosphorylation and translocation by PPARγ in HTSMCs. Mevastatin could be beneficial for prevention of airway inflammation in the future.

Antoni J Duleba - One of the best experts on this subject based on the ideXlab platform.

  • Mevastatin inhibits proliferation of rat ovarian theca interstitial cells by blocking the mitogen activated protein kinase pathway
    Fertility and Sterility, 2006
    Co-Authors: Jakub Kwintkiewicz, Nastaran Foyouzi, P Piotrowski, Izabela J Rzepczynska, Antoni J Duleba
    Abstract:

    Objective To evaluate mechanisms involved in Mevastatin-induced inhibition of proliferation of ovarian theca–interstitial cells. Design In vitro study. Setting Academic laboratory. Animal(s) Immature Sprague-Dawley female rats. Intervention(s) Ovarian theca–interstitial cells were cultured without and with Mevastatin in the presence and absence of serum, mevalonic acid, and/or insulin. Main Outcome Measure(s) Proliferation was assessed by determination of DNA synthesis by thymidine incorporation assay. Activation of extracellular signal–regulated kinase (Erk1/2) and of Akt/protein kinase B (PKB) was determined by ELISA. Result(s) Mevastatin induced a concentration-dependent inhibition of theca–interstitial cell proliferation in the absence and in the presence of serum. Inhibitory effects of Mevastatin were partly abrogated by mevalonic acid and by insulin. Mevastatin blocked basal and insulin-induced phosphorylation of ERK1/2. In contrast, Mevastatin had no significant effect on either basal or insulin-induced phosphorylation of Akt/PKB. Conclusion(s) Mevastatin inhibits proliferation of theca–interstitial cells by a mechanism that involves depletion of mevalonic acid and selective inhibition of basal and insulin-induced activity of Erk1/2 pathway, but not Akt/PKB pathway. These effects of Mevastatin may be a result of decreased isoprenylation of small GTPases.

  • Mevastatin inhibits ovarian theca interstitial cell proliferation and steroidogenesis
    Fertility and Sterility, 2004
    Co-Authors: Daniel Izquierdo, Jakub Kwintkiewicz, Nastaran Foyouzi, Antoni J Duleba
    Abstract:

    Objective Statins reduce cardiovascular risks by improving hypercholesterolemia, reducing vascular smooth muscle proliferation, and ameliorating inflammation. Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risks and is characterized by ovarian theca–interstitial hyperplasia and hyperandrogenism. This study tested the hypothesis that Mevastatin limits theca–interstitial proliferation and decreases steroidogenesis. Design In vitro study. Setting Academic laboratory. Patient(s) None. Intervention(s) Effects of Mevastatin on cultured theca–interstitial cells. Main outcome measure(s) Proliferation was evaluated by determination of DNA synthesis using thymidine incorporation assay and by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay. Production of P and T was determined by specific radioimmunoassays. Result(s) Mevastatin induced a profound concentration-dependent inhibition of DNA synthesis. At the highest concentration (30 μM), Mevastatin inhibited DNA synthesis by 92%. Similarly, in the MTT proliferation assay, Mevastatin induced a concentration-dependent decrease in cell number. Mevastatin decreased production of P (by up to 49%) and T (by up to 52%); these effects remained significant when the effect on cell culture protein content was accounted for. Conclusion(s) Mevastatin inhibits proliferation of theca–interstitial cells; it also inhibits P and T production independently of the effects on cell growth. These findings provide a foundation for studies evaluating statins as potential therapeutic agents in the treatment of ovarian mesenchymal hyperplasia and hyperandrogenism characteristic of PCOS.

Albert L Gonzales - One of the best experts on this subject based on the ideXlab platform.

Mahin Basha Syed - One of the best experts on this subject based on the ideXlab platform.

  • bioconversion of Mevastatin to pravastatin by various microorganisms and its applications a review
    Biocatalysis and agricultural biotechnology, 2018
    Co-Authors: Mahin Basha Syed, Thiruvelselvan Ponnusamy
    Abstract:

    Abstract Hypercholesterolemia is considered to be an important risk factor in coronary heart disease. Statins has received a lot of attention in recent years due to control of cholesterol biosynthesis and level of cholesterol in the body, by inhibiting the enzyme 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase. Inhibition results in reduced levels of mevalonate in the body, leading to pleiotropic effects. Compactin and its hydroxy derivative pravastatin are natural statins and are used as hypocholesterolemic agents which are potent inhibitors of HMG-CoA reductase activity. Pravastatin was more effective drug than compactin. Various fungi and bacteria have been used for the commercial production of pravastatin. Using different strategies for improving production levels, yields have been increased more than the amount originally produced. Recently, the gene sequencing is responsible for pravastatin production has been cloned and sequenced. It has been incorporated into other fungal or bacterial species for better compactin resistant as well as for maximum bioconversion rate. This review deals with the structure and chemistry, applications, mode of action, bioconversion, and production of pravastatin. This review is an effort to compile the available information on various aspects of pravastatin.

  • fermentative production and optimization of Mevastatin in submerged fermentation using aspergillus terreus
    Biotechnology Reports, 2015
    Co-Authors: Mahin Basha Syed, M Rajasimman
    Abstract:

    Abstract The main objective of the study is to enhance the Mevastatin production using Plackett–Burman (PB) and central composite design (CCD) by Aspergillus terreus in submerged fermentation (SmF). Eight nutrients were chosen for a PB design with 12 experimental runs. A maximum Mevastatin production of 170.4 mg L −1 was obtained in PB design. Response surface methodology (RSM) is a sequential procedure with an initial objective to lead the experimenter rapidly and efficiently along a path of improvement toward the general vicinity of the optimum. The individual and interactive effects of these variables were studied by conducting the fermentation run at randomly selected and different levels of all five factors. Experiments were conducted to optimize the medium constituents like glycerol, CuCl 2 ·2H 2 O, FeSO 4 ·7H 2 O, KH 2 PO 4 and MgSO 4 ·7H 2 O. At the optimum condition, a maximum Mevastatin production of 701 mg L −1 was obtained.