Inhibitory effects of luteolin and its derivatives on osteoclast differentiation and differences in luteolin production by Capsicum annuum varieties

2021 ◽  
Author(s):  
Shintaro Onishi ◽  
Shinichi Tebayashi ◽  
Yasufumi Hikichi ◽  
Hiromasa Sawada ◽  
Yukiko Ishii ◽  
...  
Keyword(s):  
Capsicum Annuum ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Plant Residue ◽  
Plant Residues ◽  
Inhibitory Effects ◽  
Effective Development ◽  
Osteoclastic Differentiation ◽  
Identification And Characterization

ABSTRACT Luteolin, an abundant flavonoid in the leaves of Capsicum annuum, has antioxidant activity and is, thus, a key chemical for promoting plant residue utilization, especially for the development of healthcare products. We assessed the inhibitory effect of luteolin and its glycosides on osteoclastic differentiation in human cells and found that the differentiation was effectively inhibited at noncytotoxic concentrations. We also screened 47 varieties of C. annuum for the accumulation of luteolin and apigenin to determine the prevalence of luteolin in diverse cultivars and identify varieties with high and/or selective luteolin production. The glycosides of luteolin and apigenin were found in all the tested varieties, with luteolin predominant over apigenin in most varieties. The identification and characterization of highly productive varieties of C. annuum is expected to be beneficial for the effective development of useful luteolin-based products from plant residues.

Genome wide identification and characterization of abiotic stress responsive lncRNAs in Capsicum annuum

2021 ◽  
Author(s):  
Pooja Moni Baruah ◽  
Debasish B. Krishnatreya ◽  
Kuntala Sarma Bordoloi ◽  
Sarvajeet Singh Gill ◽  
Niraj Agarwala
Keyword(s):  
Abiotic Stress ◽  
Capsicum Annuum ◽  
Genome Wide ◽  
Identification And Characterization

scholarly journals A Ral GAP complex links PI 3-kinase/Akt signaling to RalA activation in insulin action

2011 ◽  
Vol 22 (1) ◽  
pp. 141-152 ◽  
Author(s):  
Xiao-Wei Chen ◽  
Dara Leto ◽  
Tingting Xiong ◽  
Genggeng Yu ◽  
Alan Cheng ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Critical Role ◽  
Inhibitory Effect ◽  
Small Gtpase ◽  
Regulatory Subunit ◽  
Hydrolysis Of ◽  
Identification And Characterization

Insulin stimulates glucose transport in muscle  and adipose tissue by translocation of glucose transporter 4 (GLUT4) to the plasma membrane. We previously reported that activation of the small GTPase RalA downstream of PI 3-kinase plays a critical role in this process by mobilizing the exocyst complex for GLUT4 vesicle targeting in adipocytes. Here we report the identification and characterization of a Ral GAP complex (RGC) that mediates the activation of RalA downstream of the PI 3-kinase/Akt pathway. The complex is composed of an RGC1 regulatory subunit and an RGC2 catalytic subunit (previously identified as AS250) that directly stimulates the guanosine triphosphate hydrolysis of RalA. Knockdown of RGC proteins leads to increased RalA activity and glucose uptake in adipocytes. Insulin inhibits the GAP complex through Akt2-catalyzed phosphorylation of RGC2 in vitro and in vivo, while activated Akt relieves the inhibitory effect of RGC proteins on RalA activity. The RGC complex thus connects PI 3-kinase/Akt activity to the transport machineries responsible for GLUT4 translocation.

MO058INHIBITION OF OSTEOCLAST DIFFERENTIATION BY 1.25-D AND THE CALCIMIMETIC KP2326 REVEALS 1.25-D RESISTANCE IN ADVANCED CKD

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Julie Bernardor ◽  
Sacha Flammier ◽  
Bruno Ranchin ◽  
Segolene Gaillard ◽  
Diane Platel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Active Vitamin ◽  
Vitamin D Analogs ◽  
Active Vitamin D ◽  
Ckd Stage ◽  
Osteoclastic Differentiation

Abstract Background and Aims Active vitamin D analogs and calcimimetics are cornerstones for managing secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). Their direct effects on bone cells remain to be determined. Method Peripheral blood mononuclear cells (PBMCs) of 19 pediatric CKD patients and 6 healthy donors (HD) were differentiated into osteoclasts in presence of M-CSF and RANKL. Effect of combined or single treatment with active vitamin D (1.25-D) and/or the calcimimetic KP2326 were evaluated onto osteoclast differentiation and osteoclast mediated bone resorption. Results 1.25-D inhibited osteoclastic differentiation, a significant resistance to 1.25-D was observed when CKD worsens. A significant albeit less important inhibitory effect of KP2326 on osteoclastic differentiation was also found both in cells derived from HD and CKD patients, through an activation of the Erk pathway. This inhibitory effect was not modified by CKD stage. Combinatorial treatment with 1.25-D and KP2326 did not result in synergistic effects. Last, KP2326 significantly inhibited human osteoclast-mediated bone resorption. Conclusion Both 1.25-D and KP2326 inhibit osteoclastic differentiation, however to a different extent. Whilst 1.25-D has no significant effect on bone resorption, KP2326 inhibits bone resorption. Recent data showed that calcimimetics also have a direct anabolic effect on bone, through the stimulation of osteoblastic differentiation and mineralization in human mesenchymal stem cells in vitro. All these results provide a strong rationale for a global positive effect of calcimimetics on bone remodeling. Calcimimetics also significantly decrease FGF23 levels. In the setting of global systematic deleterious effects of high FGF23 levels in CKD, and keeping in mind that active vitamin D analogs stimulate FGF 23 production, all these data could favor the use of decreased doses of 1.25-D with low-doses of calcimimetics in SHPT in dialysis, the combination of these two therapies already being proposed in the 2017 K-DIGO guidelines.

scholarly journals Identification and Characterization of Zika Virus NS5 Methyltransferase Inhibitors

2021 ◽  
Vol 11 ◽  
Author(s):  
Weibao Song ◽  
Hongjuan Zhang ◽  
Yu Zhang ◽  
Ying Chen ◽  
Yuan Lin ◽  
...  
Keyword(s):  
Zika Virus ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Site Directed Mutagenesis ◽  
Structural Protein ◽  
Mtase Activity ◽  
Natural Product Library ◽  
Dose Dependent ◽  
Identification And Characterization

The recurring outbreak of Zika virus (ZIKV) worldwide makes an emergent demand for novel, safe and efficacious anti-ZIKV agents. ZIKV non-structural protein 5 (NS5) methyltransferase (MTase), which is essential for viral replication, is regarded as a potential drug target. In our study, a luminescence-based methyltransferase assay was used to establish the ZIKV NS5 MTase inhibitor screening model. Through screening a natural product library, we found theaflavin, a polyphenol derived from tea, could inhibit ZIKV NS5 MTase activity with a 50% inhibitory concentration (IC50) of 10.10 μM. Molecular docking and site-directed mutagenesis analyses identified D146 as the key amino acid in the interaction between ZIKV NS5 MTase and theaflavin. The SPR assay indicated that theaflavin had a stronger binding activity with ZIKV NS5 wild-type (WT)-MTase than it with D146A-MTase. Moreover, theaflavin exhibited a dose dependent inhibitory effect on ZIKV replication with a 50% effective concentration (EC50) of 8.19 μM. All these results indicate that theaflavin is likely to be a promising lead compound against ZIKV.

Identification and characterization of gelatin-cleavage activities in the apically located extracellular matrix of the sea urchin embryo

2000 ◽  
Vol 78 (4) ◽  
pp. 455-462 ◽  
Author(s):  
Justin Flood ◽  
Janice Mayne ◽  
John J Robinson
Keyword(s):  
Extracellular Matrix ◽  
Sea Urchin ◽  
Inhibitory Effect ◽  
Divalent Metal Ions ◽  
Gelatinase Activity ◽  
Sea Urchin Embryo ◽  
Phenylmethyl Sulfonyl Fluoride ◽  
Sulfonyl Fluoride ◽  
Identification And Characterization

We have identified and partially characterized several gelatinase activities associated with the sea urchin extraembryonic matrix, the hyaline layer. A previously identified 41-kDa collagenase/gelatinase activity was generally not found to be associated with isolated hyaline layers but was dissociated from the surface of 1-h-old embryos in the absence of Ca2+ and Mg2+. While hyaline layers, freshly prepared from 1-h-old embryos, were devoid of any associated gelatinase activities, upon storage at 4°C for 4 days, a number of gelatin-cleavage activities appeared. Comparative analysis of these activities with the 41-kDa collagenase/gelatinase revealed that all species were inhibited by ethylenediamine tetraacetic acid but were refractory to inhibition with the serine protease inhibitors, phenylmethyl sulfonyl fluoride and benzamidine. In contrast, the largely Zn2+ specific chelator 1,10-phenanthroline had markedly different effects on the gelatinase activities. While several of the storage-induced, hyaline-layer-associated gelatinase activities were inhibited, the 41-kDa collagenase/gelatinase was refractory to inhibition as was a second gelatinase species with an apparent molecular mass of 45 kDa. We also examined the effects of a series of divalent metal ions on the gelatin-cleavage activities. In both qualitative and quantitative assays, Ca2+ was the most effective activator while Mn2+, Cu2+, Cd2+, and Zn2+ were all inhibitory. In contrast, Mg2+ had a minimal inhibitory effect on storage-induced gelatinase activities but significantly inhibited the 41-kDa collagenase/gelatinase. These results identify several distinct gelatin-cleavage activities associated with the sea urchin extraembryonic hyaline layer and point to diversity in the biochemical nature of these species.Key words: gelatinase, sea urchin, extracellular matrix.

scholarly journals Identification and Characterization of Mutations Conferring Resistance to d-Amino Acids in Bacillus subtilis

2015 ◽  
Vol 197 (9) ◽  
pp. 1632-1639 ◽  
Author(s):  
Sara A. Leiman ◽  
Charles Richardson ◽  
Lucy Foulston ◽  
Alexander K. W. Elsholz ◽  
Eric A. First ◽  
...  
Keyword(s):  
Amino Acids ◽  
Bacillus Subtilis ◽  
Protein Biosynthesis ◽  
Trna Synthetase ◽  
Inhibitory Effects ◽  
Content Type ◽  
Growth Inhibitory ◽  
Spontaneous Mutants ◽  
Identification And Characterization

ABSTRACTBacteria produced-amino acids for incorporation into the peptidoglycan and certain nonribosomally produced peptides. However,d-amino acids are toxic if mischarged on tRNAs or misincorporated into protein. Common strains of the Gram-positive bacteriumBacillus subtilisare particularly sensitive to the growth-inhibitory effects ofd-tyrosine due to the absence ofd-aminoacyl-tRNA deacylase, an enzyme that prevents misincorporation ofd-tyrosine and otherd-amino acids into nascent proteins. We isolated spontaneous mutants ofB. subtilisthat survive in the presence of a mixture ofd-leucine,d-methionine,d-tryptophan, andd-tyrosine. Whole-genome sequencing revealed that these strains harbored mutations affecting tRNATyrcharging. Three of the most potent mutations enhanced the expression of the gene (tyrS) for tyrosyl-tRNA synthetase. In particular, resistance was conferred by mutations that destabilized the terminator hairpin of thetyrSriboswitch, as well as by a mutation that transformed a tRNAPheinto atyrSriboswitch ligand. The most potent mutation, a substitution near the tyrosine recognition site of tyrosyl-tRNA synthetase, improved enzyme stereoselectivity. We conclude that these mutations promote the proper charging of tRNATyr, thus facilitating the exclusion ofd-tyrosine from protein biosynthesis in cells that lackd-aminoacyl-tRNA deacylase.IMPORTANCEProteins are composed ofl-amino acids. Mischarging of tRNAs withd-amino acids or the misincorporation ofd-amino acids into proteins causes toxicity. This work reports on mutations that confer resistance tod-amino acids and their mechanisms of action.

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