scholarly journals Lepidopteran HMG-CoA reductase is a potential selective target for pest control

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2881 ◽  
Author(s):  
Yuan-mei Li ◽  
Zhen-peng Kai ◽  
Juan Huang ◽  
Stephen S. Tobe
Keyword(s):  
Sequence Alignment ◽  
Pest Control ◽  
Lethal Effect ◽  
Structural Comparison ◽  
Hmg Coa Reductase ◽  
Regulatory Effects ◽  
Negative Impacts ◽  
Coa Reductase ◽  
Selective Insecticide

As a consequence of the negative impacts on the environment of some insecticides, discovery of eco-friendly insecticides and target has received global attention in recent years. Sequence alignment and structural comparison of the rate-limiting enzyme HMG-CoA reductase (HMGR) revealed differences between lepidopteran pests and other organisms, which suggested insect HMGR could be a selective insecticide target candidate. Inhibition of JH biosynthesis in vitro confirmed that HMGR inhibitors showed a potent lethal effect on the lepidopteran pest Manduca sexta, whereas there was little effect on JH biosynthesis in Apis mellifera and Diploptera punctata. The pest control application of these inhibitors demonstrated that they can be insecticide candidates with potent ovicidal activity, larvicidal activity and insect growth regulatory effects. The present study has validated that Lepidopteran HMGR can be a potent selective insecticide target, and the HMGR inhibitors (especially type II statins) could be selective insecticide candidates and lead compounds. Furthermore, we demonstrated that sequence alignment, homology modeling and structural comparison may be useful for determining potential enzymes or receptors which can be eco-friendly pesticide  targets.

In vitro antioxidant, antiglycation, and enzymatic inhibitory activity against α-glucosidase, α-amylase, lipase and HMG-CoA reductase of Terminalia boivinii Tul.

2021 ◽  
pp. 102235
Author(s):  
Bongani Sicelo Dlamini ◽  
Carlos Eduardo Hernandez ◽  
Chiy-Rong Chen ◽  
Wen-Ling Shih ◽  
Jue-Liang Hsu ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Hmg Coa Reductase ◽  
Coa Reductase

scholarly journals An autonomous, but INSIG-modulated, role for the Sterol Sensing Domain in mallostery-regulated ERAD of yeast HMG-CoA reductase

2020 ◽  
pp. jbc.RA120.015910
Author(s):  
Margaret A Wangeline ◽  
Randolph Y Hampton
Keyword(s):  
Binding Site ◽  
Quaternary Structure ◽  
Limited Proteolysis ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
Level Analysis

HMG-CoA reductase (HMGR) undergoes feedback-regulated degradation as part of sterol pathway control. Degradation of the yeast HMGR isozyme Hmg2 is controlled by the sterol pathway intermediate GGPP, which causes misfolding of Hmg2, leading to degradation by the HRD pathway; we call this process mallostery. We evaluated the role of the Hmg2 sterol sensing domain (SSD) in mallostery, as well as the involvement of the highly conserved INSIG proteins. We show that the Hmg2 SSD is critical for regulated degradation of Hmg2 and required for mallosteric misfolding of GGPP as studied by in vitro limited proteolysis. The Hmg2 SSD functions independently of conserved yeast INSIG proteins, but its function was modulated by INSIG, thus imposing a second layer of control on Hmg2 regulation. Mutant analyses indicated that SSD-mediated mallostery occurred prior to and independent of HRD-dependent ubiquitination. GGPP-dependent misfolding was still extant but occurred at a much slower rate in the absence of a functional SSD, indicating that the SSD facilitates a physiologically useful rate of GGPP response, and implying that the SSD is not a binding site for GGPP. Non-functional SSD mutants allowed us to test the importance of Hmg2 quaternary structure in mallostery:  a non-responsive Hmg2 SSD mutant strongly suppressed regulation of a co-expressed, normal Hmg2. Finally, we have found that GGPP-regulated misfolding occurred in detergent-solubilized Hmg2, a feature that will allow next-level analysis of the mechanism of this novel tactic of ligand-regulated misfolding.

scholarly journals An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro

Circulation ◽  
2001 ◽  
Vol 103 (2) ◽  
pp. 276-283 ◽  
Author(s):  
Masanori Aikawa ◽  
Elena Rabkin ◽  
Seigo Sugiyama ◽  
Sami J. Voglic ◽  
Yoshihiro Fukumoto ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Tissue Factor ◽  
Reductase Inhibitor ◽  
Hmg Coa Reductase ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase

scholarly journals Bark Extracts of Ceylon Cinnamon Possess Antilipidemic Activities and Bind Bile Acids In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Walimuni Prabhashini Kaushalya Mendis Abeysekera ◽  
Sirimal Premakumara Galbada Arachchige ◽  
Wanigasekera Daya Ratnasooriya
Keyword(s):  
Bile Acids ◽  
Scientific Evidence ◽  
Ethanol Extract ◽  
Cholesterol Esterase ◽  
Hmg Coa Reductase ◽  
Cinnamon Bark ◽  
Ceylon Cinnamon ◽  
Inhibitory Activities ◽  
Coa Reductase

Ethanol (95%) and dichloromethane : methanol (1 : 1) bark extracts of authenticated Ceylon cinnamon were investigated for range of antilipidemic activities (ALA): HMG-CoA reductase, lipase, cholesterol esterase, and cholesterol micellization inhibitory activities and bile acids binding in vitro. Individual compounds in bark extracts were also evaluated. Bark extracts showed ALA in all the assays studied. The IC50 (μg/mL) values ranged within 153.07±8.38–277.13±32.18, 297.57±11.78–301.09±4.05, 30.61±0.79–34.05±0.41, and 231.96±9.22–478.89±9.27, respectively, for HMG-CoA reductase, lipase, cholesterol esterase, and cholesterol micellization inhibitory activities. The bile acids binding (3 mg/mL) for taurocholate, glycodeoxycholate, and chenodeoxycholate ranged within 19.74±0.31–20.22±0.31, 21.97±2.21–26.97±1.61, and 16.11±1.42–19.11±1.52%, respectively. The observed ALA were moderate compared to the reference drugs studied. Individual compounds in bark extracts ranged within 2.14±0.28–101.91±3.61 and 0.42±0.03–49.12±1.89 mg/g of extract. Cinnamaldehyde and gallic acid were the highest and the lowest among the tested compounds. The ethanol extract had highest quantity of individual compounds and ALA investigated. Properties observed indicate usefulness of Ceylon cinnamon bark in managing hyperlipidemia and obesity worldwide. Further, this study provides scientific evidence for the traditional claim that Ceylon cinnamon has antilipidemic activities.

scholarly journals Molecular cloning and sequence of a cholesterol-repressible enzyme related to prenyltransferase in the isoprene biosynthetic pathway.

1987 ◽  
Vol 7 (9) ◽  
pp. 3138-3146 ◽  
Author(s):  
C F Clarke ◽  
R D Tanaka ◽  
K Svenson ◽  
M Wamsley ◽  
A M Fogelman ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Amino Acid ◽  
Molecular Cloning ◽  
In Vitro Transcription ◽  
In Vitro Translation ◽  
Mrna Levels ◽  
Hmg Coa Reductase ◽  
Transcription System ◽  
Coa Reductase

Differential hybridization and molecular cloning have been used to isolate CR39, a cDNA which hybridizes to a 1.2-kilobase (kb) mRNA in rat liver. The level of CR39 mRNA was increased seven- to ninefold over normal levels by dietary cholestyramine and mevinolin and decreased about fourfold compared with normal levels by cholesterol feeding or administration of mevalonate. Similar changes in the mRNA levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and HMG-CoA synthase were observed under the various conditions. In vitro translation of either CR39 hybrid selected RNA or 1.2-kb CR39 RNA generated by an SP6 in vitro transcription system produced a polypeptide of 39,000 daltons. As deduced from the nucleotide sequence of a full-length CR39 cDNA, the rat CR39 polypeptide contained 344 amino acids and had a molecular weight of 39,615. The predicted amino acid composition and submit molecular weight of the rat CR39 were very similar to those of prenyltransferases isolated from chicken, pig, and human. The sequence of amino acid residues 173 through 203 in the rat CR39 polypeptide showed that 17 out of 30 matched an active-site peptide of avian liver prenyltransferase. Thus, alterations in the rate of cholesterogenesis resulted in the coordinate regulation of three mRNAs encoding HMG-CoA reductase, HMG-CoA synthase, and CR39, the latter being tentatively identified as prenyltransferase.

scholarly journals Identification, Evolution, and Essentiality of the Mevalonate Pathway for Isopentenyl Diphosphate Biosynthesis in Gram-Positive Cocci

2000 ◽  
Vol 182 (15) ◽  
pp. 4319-4327 ◽  
Author(s):  
E. Imogen Wilding ◽  
James R. Brown ◽  
Alexander P. Bryant ◽  
Alison F. Chalker ◽  
David J. Holmes ◽  
...  
Keyword(s):  
Mevalonate Pathway ◽  
Genomic Analysis ◽  
Eukaryotic Cell ◽  
Infection Model ◽  
Isopentenyl Diphosphate ◽  
Gram Positive ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
Gram Positive Cocci

ABSTRACT The mevalonate pathway and the glyceraldehyde 3-phosphate (GAP)–pyruvate pathway are alternative routes for the biosynthesis of the central isoprenoid precursor, isopentenyl diphosphate. Genomic analysis revealed that the staphylococci, streptococci, and enterococci possess genes predicted to encode all of the enzymes of the mevalonate pathway and not the GAP-pyruvate pathway, unlike Bacillus subtilis and most gram-negative bacteria studied, which possess only components of the latter pathway. Phylogenetic and comparative genome analyses suggest that the genes for mevalonate biosynthesis in gram-positive cocci, which are highly divergent from those of mammals, were horizontally transferred from a primitive eukaryotic cell. Enterococci uniquely encode a bifunctional protein predicted to possess both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and acetyl-CoA acetyltransferase activities. Genetic disruption experiments have shown that five genes encoding proteins involved in this pathway (HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, and mevalonate diphosphate decarboxylase) are essential for the in vitro growth of Streptococcus pneumoniae under standard conditions. Allelic replacement of the HMG-CoA synthase gene rendered the organism auxotrophic for mevalonate and severely attenuated in a murine respiratory tract infection model. The mevalonate pathway thus represents a potential antibacterial target in the low-G+C gram-positive cocci.

Pravastatin increases the expression of the tissue inhibitor of matrix metalloproteinase-1 and the oncogeneBaxin human aortic abdominal aneurysms

2008 ◽  
Vol 86 (7) ◽  
pp. 431-437 ◽  
Author(s):  
Petra J. Mateos-Cáceres ◽  
Antonio J. López-Farré ◽  
Pilar C. Morata ◽  
Priscila Ramos-Mozo ◽  
Carlos Macaya ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Apoptotic Index ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor ◽  
Hmg Coa Reductase ◽  
Matrix Metalloproteinase 1 ◽  
Abdominal Aortic ◽  
Coa Reductase ◽  
Metalloproteinase 9

The effect of pravastatin on matrix metalloproteinase-9 (MMP-9) and the level of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 was studied in explants of human abdominal aortic aneurysm (AAA) obtained from 13 patients. The effect of pravastatin on the apoptotic status of human AAA explants was also examined. Total MMP-9 content did not differ in human AAA explants incubated in vitro in the presence or absence of pravastatin (10−6mol/L) for 48 h. TIMP-1 levels were significantly increased in pravastatin-incubated AAA explants, but TIMP-2 production was not modified by pravastatin. Western blot experiments showed that, whereas Bax expression was increased in pravastatin-incubated AAA explants, the expression of Bcl-2 was not modified. On the other hand, the ratio of the expression of Bax to Bcl-2, an apoptotic index, was not modified by pravastatin. In the human AAA explants, the increase in Bax expression, but not the increase in TIMP-1 expression elicited by pravastatin, was reversed by l-mevalonate, a downstream HMG-CoA reductase metabolite, suggesting that the expression of Bax and TIMP-1 followed HMG-CoA reductase-dependent and -independent pathways, respectively. In conclusion, pravastatin increases both TIMP-1 and Bax expression in human AAA explants without changes in either MMP-9 activity or the apoptotic status.

Sign in / Sign up

Export Citation Format

Share Document