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101.
Richardson TI Norman BH Lugar CW Jones SA Wang Y Durbin JD Krishnan V Dodge JA 《Bioorganic & medicinal chemistry letters》2007,17(13):3570-3574
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe structure-activity relationship studies that led to the discovery of bezopyran 5b. X-ray crystal structures of 5b and a non-selective analog 5c in ERalpha help explain the observed selectivity of the benzopyran platform. 相似文献
102.
Krishnan AV Moreno J Nonn L Malloy P Swami S Peng L Peehl DM Feldman D 《The Journal of steroid biochemistry and molecular biology》2007,103(3-5):694-702
Calcitriol, the hormonally active form of Vitamin D, inhibits the growth and development of many cancers through multiple mechanisms. Our recent research supports the contributory role of several new and diverse pathways that add to the mechanisms already established as playing a role in the actions of calcitriol to inhibit the development and progression of prostate cancer (PCa). Calcitriol increases the expression of insulin-like growth factor binding protein-3 (IGFBP-3), which plays a critical role in the inhibition of PCa cell growth by increasing the expression of the cell cycle inhibitor p21. Calcitriol inhibits the prostaglandin (PG) pathway by three actions: (i) the inhibition of the expression of cyclooxygenase-2 (COX-2), the enzyme that synthesizes PGs, (ii) the induction of the expression of 15-prostaglandin dehydrogenase (15-PGDH), the enzyme that inactivates PGs and (iii) decreasing the expression of EP and FP PG receptors that are essential for PG signaling. Since PGs have been shown to promote carcinogenesis and progression of multiple cancers, the inhibition of the PG pathway may add to the ability of calcitriol to prevent and inhibit PCa development and growth. The combination of calcitriol and non-steroidal anti-inflammatory drugs (NSAIDs) result in a synergistic inhibition of PCa cell growth and offers a potential therapeutic strategy. Mitogen activated protein kinase phosphatase 5 (MKP5) is a member of a family of phosphatases that are negative regulators of MAP kinases. Calcitriol induces MKP5 expression in prostate cells leading to the selective dephosphorylation and inactivation of the stress-activated kinase p38. Since p38 activation is pro-carcinogenic and is a mediator of inflammation, this calcitriol action, especially coupled with the inhibition of the PG pathway, contributes to the chemopreventive activity of calcitriol in PCa. Mullerian Inhibiting Substance (MIS) has been evaluated for its inhibitory effects in cancers of the reproductive tissues and is in development as an anti-cancer drug. Calcitriol induces MIS expression in prostate cells revealing yet another mechanism contributing to the anti-cancer activity of calcitriol in PCa. Thus, we conclude that calcitriol regulates myriad pathways that contribute to the potential chemopreventive and therapeutic utility of calcitriol in PCa. 相似文献
103.
Thilakaraj R Raghunathan K Anishetty S Pennathur G 《Bioinformatics (Oxford, England)》2007,23(3):267-271
Metal ion binding domains are found in proteins that mediate transport, buffering or detoxification of metal ions. In this study, we have performed an in silico analysis of metal binding proteins and have identified putative metal binding motifs for the ions of cadmium, cobalt, zinc, arsenic, mercury, magnesium, manganese, molybdenum and nickel. A pattern search against the UniProtKB/Swiss-Prot and UniProtKB/TrEMBL databases yielded true positives in each case showing the high-specificity of the motifs. Motifs were also validated against PDB structures and site directed mutagenesis studies. 相似文献
104.
Garver WS Jelinek D Oyarzo JN Flynn J Zuckerman M Krishnan K Chung BH Heidenreich RA 《Journal of cellular biochemistry》2007,101(2):498-516
Niemann-Pick type C1 (NPC1) disease is an autosomal-recessive cholesterol-storage disorder characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. The NPC1 gene is expressed in every tissue of the body, with liver expressing the highest amounts of NPC1 mRNA and protein. A number of studies have now indicated that the NPC1 protein regulates the transport of cholesterol from late endosomes/lysosomes to other cellular compartments involved in maintaining intracellular cholesterol homeostasis. The present study characterizes liver disease and lipid metabolism in NPC1 mice at 35 days of age before the development of weight loss and neurological symptoms. At this age, homozygous affected (NPC1(-/-)) mice were characterized with mild hepatomegaly, an elevation of liver enzymes, and an accumulation of liver cholesterol approximately four times that measured in normal (NPC1(+/+)) mice. In contrast, heterozygous (NPC1(+/-)) mice were without hepatomegaly and an elevation of liver enzymes, but the livers had a significant accumulation of triacylglycerol. With respect to apolipoprotein and lipoprotein metabolism, the results indicated only minor alterations in NPC1(-/-) mouse serum. Finally, compared to NPC1(+/+) mouse livers, the amount and processing of SREBP-1 and -2 proteins were significantly increased in NPC1(-/-) mouse livers, suggesting a relative deficiency of cholesterol at the metabolically active pool of cholesterol located at the endoplasmic reticulum. The results from this study further support the hypothesis that an accumulation of lipoprotein-derived cholesterol within late endosomes/lysosomes, in addition to altered intracellular cholesterol homeostasis, has a key role in the biochemical and cellular pathophysiology associated with NPC1 liver disease. 相似文献
105.
Krishnan N Vecera J Kodrík D Sehnal F 《Archives of insect biochemistry and physiology》2007,65(3):114-124
Injections of 38 pmol paraquat (1,1'-dimethyl-4,4'-bypyridilium) into adult Pyrrhocoris apterus (average body weight 29.6 mg in males and 36.9 mg in females) caused a significant elevation of lipid peroxidation and protein carbonylation and a decline of membrane fluidity in the microsomal brain fraction. Another manifestation of oxidative stress was a depletion of the reduced glutathione pool and reduction of the gamma-glutamyl transpeptidase activity in the brain extracts. The damaging action of paraquat on the brain was counteracted by simultaneous injection of 1 pmol 20-hydroxyecdysone (20E). 20E restrained lipid peroxidation and the formation of protein carbonyls, ameliorated changes in microsomal membrane fluidity, enhanced the level of reduced glutathione, and upregulated the activity of gamma-glutamyl transpeptidase. At the organismic level, 20E curtailed three detrimental effects caused by paraquat injection: the disappearance of a blood protein, the suppression of fecundity and egg hatchability, and the shortening of adult life span. The data showed that 20E provided a systemic antioxidant protection but the significance of endogenous ecdysteroids in the management of oxidative stress remains to be shown. 相似文献
106.
107.
Growth factors upregulate deposition and remodeling of ECM by endothelial cells cultured for tissue-engineering applications 总被引:1,自引:0,他引:1
Appropriate matrix formation, turnover and remodeling in tissue-engineered small diameter vascular conduits are crucial for their long-term function. The interaction between cells and extra-cellular components is indispensable in determining cellular behavior in tissues and on biomaterials. The fibrin that contains fibronectin shows promise in most aspects as a tissue engineering scaffold, whereas, deposition of elastin and collagen by endothelial cells grown in the lumen of the construct is desirable to improve post implant retention, mechanical stability and vaso-responsiveness. So far there is no report on production of extra-cellular matrix (ECM) proteins, elastin and collagen by endothelial cells (EC) in in vitro culture conditions. In this study, we have used a biomimetic approach of providing multiple growth factors (GF) in the fibronectin (FN)-containing fibrin matrix to induce production of elastin and collagen by the endothelial cells for application in vascular tissue engineering. Deposition of elastin and collagens with matrix remodeling is demonstrated through qualitative analysis of the matrices that were recovered after growing cells on the initial fibrin-FN-GF matrix. Expressions of mRNA for both proteins were assessed by real time polymerase chain reaction (RT-PCR) to estimate the effects of multiple growth factor compositions. Marked deposition of elastin and collagen was evidenced by staining the recovered matrix after different culture intervals. Obviously, the biomimetic environment created by adding angiogenic and platelet growth factors in the fibrin-fibronectin-gelatin matrix can induce deposition of collagens and elastin by EC. 相似文献
108.
Patidar Preeti Bhayal Mamta Hajela Sumati Hajela Krishnan 《Journal of plant biochemistry and biotechnology.》2022,31(4):961-964
Journal of Plant Biochemistry and Biotechnology - A glycosylated heat stable trypsin chymotrypsin inhibitor was isolated from Cyamopsis tetragonoloba seeds. It is being reported for the first time... 相似文献
109.
Analysis of Pathogenic Diversity of the Rice Bacterial Blight Pathogen (Xanthomonas oryzae pv. oryzae) in the Andaman Islands and Identification of Effective Resistance Genes
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Raj K. Gautam Pankaj K. Singh Krishnan Sakthivel Muthulingam Srikumar Naresh Kumar Krishna Kumar Awnindra K. Singh Sibnarayan Dam Roy 《Journal of Phytopathology》2015,163(6):423-432
Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is a major disease of rice in the tropics for which genetic resistance in the host plants is the only effective solution. This study aimed at identification of resistance gene combinations effective against Xoo isolates and fingerprinting of the Xoo isolates of Andaman Islands (India). Here, we report the reaction of 21 rice BB differentials possessing Xa1 to Xa21 genes individually and in different combinations to various isolates of pathogen collected from Andaman Islands. Pathological screening results of 14 isolates revealed that among individual genes tested across 2 years, Xa4, Xa7 and Xa21 conferred resistance reaction across all isolates, whereas among combinations, IRBB 50 (Xa4 + xa5), IRBB 52 (Xa4 + Xa21) and IRBB 60 (Xa4 + xa5 + xa13 + Xa21) conveyed effective resistance against tested isolates. The nature of genetic diversity among four isolates selected on the basis of geographical isolation in the islands was studied through DNA finger printing. The RAPD primers S111, S119, S1117, S1109, S1103, S109 and S105 were found to be better indicators of molecular diversity among isolates than JEL primers. The diversity analysis grouped 14 isolates into three major clusters based on disease reaction wherein isolate no. 8 was found the most divergent as well as highly virulent. The remaining isolates were classified into two distinct groups. The importance of the study in the context of transfer of resistance gene(s) in the local cultivars specifically for tropical island conditions is presented and discussed. 相似文献
110.
A novel intrinsically fluorescent probe for study of uptake and trafficking of 25-hydroxycholesterol