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81.
Endothelial cell barrier protection by simvastatin: GTPase regulation and NADPH oxidase inhibition 总被引:1,自引:0,他引:1
Chen W Pendyala S Natarajan V Garcia JG Jacobson JR 《American journal of physiology. Lung cellular and molecular physiology》2008,295(4):L575-L583
The statins, hydroxy-3-methylglutaryl-CoA reductase inhibitors that lower serum cholesterol, exhibit myriad clinical benefits, including enhanced vascular integrity. One potential mechanism underlying increased endothelial cell (EC) barrier function is inhibition of geranylgeranylation, a covalent modification enabling translocation of the small GTPases Rho and Rac to the cell membrane. While RhoA inhibition attenuates actin stress fiber formation and promotes EC barrier function, Rac1 inhibition at the cell membrane potentially prevents activation of NADPH oxidase and subsequent generation of superoxides known to induce barrier disruption. We examined the relative regulatory effects of simvastatin on RhoA, Rac1, and NADPH oxidase activities in the context of human pulmonary artery EC barrier protection. Confluent EC treated with simvastatin demonstrated significantly decreased thrombin-induced FITC-dextran permeability, a reflection of vascular integrity, which was linked temporally to simvastatin-mediated actin cytoskeletal rearrangement. Compared with Rho inhibition alone (Y-27632), simvastatin afforded additional protection against thrombin-mediated barrier dysfunction and attenuated LPS-induced EC permeability and superoxide generation. Statin-mediated inhibition of both Rac translocation to the cell membrane and superoxide production were attenuated by geranylgeranyl pyrophosphate (GGPP), indicating that these effects are due to geranylgeranylation inhibition. Finally, thrombin-induced EC permeability was modestly attenuated by reduced Rac1 expression (small interfering RNA), whereas these effects were made more pronounced by simvastatin pretreatment. Together, these data suggest EC barrier protection by simvastatin is due to dual inhibitory effects on RhoA and Rac1 as well as the attenuation of superoxide generation by EC NADPH oxidase and contribute to the molecular mechanistic understanding of the modulation of EC barrier properties by simvastatin. 相似文献
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Vimaleswaran KS Radha V Ramya K Babu HN Savitha N Roopa V Monalisa D Deepa R Ghosh S Majumder PP Rao MR Mohan V 《Human genetics》2008,123(6):599-605
Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective
of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type
2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated
subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin
levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (−11377C→G and −11282T→C), one intronic
SNP (+10211T→G) and one exonic SNP (+45T→G) by SSCP and direct sequencing in a pilot study (n = 500). The +10211T→G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed
that subjects with TG genotype of +10211T→G had significantly higher risk for diabetes compared to TT genotype [Odds ratio
1.28; 95% Confidence Interval (CI) 1.07–1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype (P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was
1.53 (95%CI 1.3–1.8; P < 10−7) and that for GG genotype, 2.10 (95% CI 1.3–3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG (P = 0.007) and TG (P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T→G polymorphism in the
first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia. 相似文献
84.
R. Viswanathan 《BMJ (Clinical research ed.)》1936,2(3964):1300-1302
85.
Elangovan Elamathi Palaniyandi Malathi Rasappa Viswanathan Amalraj Ramesh Sundar 《Journal of plant biochemistry and biotechnology.》2018,27(3):351-361
Present study was aimed to select a suitable Trichoderma isolate as candidate antagonist based on its efficacy in producing cell wall degrading enzymes (CWDEs), its mycoparasitism activity and expression of related genes against the red rot pathogen caused by Colletotrichum falcatum in sugarcane. For which, six different isolates of Trichoderma selected from our earlier studies (T. harzianum, T. asperullum) were evaluated based on their capability in releasing cell wall degrading enzymes individually and during antagonism with C. falcatum in dual plate. Amongst T. harzianum (T20) exhibited the greatest mycoparasitic potential against the C. falcatum, by producing higher concentration of CWDEs viz., chitinase and β-1, 3-glucanase, slightly lower amounts of cellulase and protease with significant reduction in polygalacturonase produced by pathogen. Further microscopic observation on interaction of C. falcatum with the selected isolate of T. harzianum (T20) exhibited the mycoparasitic activity of antagonist over pathogen in dual culture and inhibition of C. falcatum pathogenesis in detached sugarcane leaves. In addition, expression pattern of eight genes coding various enzymes involved in mycoparasitism by T. harzianum over C. falcatum were analyzed using qRT-PCR in vitro and on sugarcane leaves. In in vitro interactions, five genes of cell wall degrading enzymes viz., chitinase (chit33), endochitinase (endo42), β-1, 3-glucanase (glu), exochitinase 1 (exc1), exochitinase 2 (exc2), were upregulated during and after contact as compared to before contact, while three genes related with proteases such as alkaline proteinase (prb1), trypsin-like protease (Pra1), subtilin-like serine protease (ssp), genes were upregulated during the contact with C. falcatum and slightly down regulated after contact. In detached leaves, seven genes were potentially upregulated except subtilin-like serine protease, which was down regulated during interaction of C. falcatum and T. harzianum as compared to T. harzianum inoculation alone. All these biochemical and molecular results confirm the efficacy of T. harzianum (T20) against C. falcatum and justify the right selection of candidate antagonist for our further studies on identification of antifungal genes/proteins against C. falcatum in sugarcane. 相似文献
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88.
Nuclear lipid mediators: Role of nuclear sphingolipids and sphingosine‐1‐phosphate signaling in epigenetic regulation of inflammation and gene expression 下载免费PDF全文
89.
The aqueous solution equilibria and solute structure of vitamin B6 compounds and several model compounds have been investigated using 13C-nmr spectroscopy. The unsubstituted α-carbon of these compounds is a very good probe for data which permits assignment of the ionization steps to indicidual groups. While the ionizations of the pyridinium and phenolic groups take place simultaneously in 3-hydroxypyridine, they take place in well-separated steps in pyridoxamine (PM), pyridoxamine phosphate (PMP), and pyridoxal phosphate. It has been established that the ionization with a pKa value of 3.7 is predominantly phenolic in origin in PM and PMP. A zwitterionic structure consistent with the earlier spectroscopic investigations is proposed for the vitamin B6 compounds in neutral aqueous solution. 相似文献
90.