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91.
Jozaa Z. ALTamimi Nora A. AlFaris Dalal H. Aljabryn Reham I. Alagal Ghedeir M. Alshammari Hussain Aldera Sultan Alqahtani Mohammed Abdo Yahya 《Saudi Journal of Biological Sciences》2021,28(8):4300-4310
Diabetes mellitus induces testicular damage, increases sperm abnormalities, and impairs reproductive dysfunction due to induction of endocrine disturbance and testicular oxidative stress. This study evaluated the reproductive protective effect of ellagic acid (EA) against testicular damage and abnormalities in sperm parameters in Streptozotocin (STZ)-induced diabetic rats (T1DM) and examined some possible mechanisms of protection. Adult male rats were segregated into 5 groups (n = 12 rat/each) as control, control + EA (50 mg/kg/day), T1DM, T1DM + EA, and T1DM + EA + brusatol (an Nrf-2 inhibitor) (2 mg/twice/week). All treatments were conducted for 12 weeks, daily. EA preserved the structure of the seminiferous tubules, prevented the reduction in sperm count, motility, and viability, reduced sperm abnormalities, and downregulated testicular levels of cleaved caspase-3 and Bax in diabetic rats. In the control and diabetic rats, EA significantly increased the circulatory levels of testosterone, reduced serum levels of FSH and LH, and upregulated Bcl-2 and all steroidogenic genes (StAr, 3β-HSD1, and 11β-HSD1). Besides, it reduced levels of ROS and MDA but increased levels of GSH and MnSOD and the transactivation of Nrf2. All these biochemical alterations induced by EA were associated with increased activity and nuclear accumulation of Nrf2. However, all these effects afforded by EA were weakened in the presence of brusatol. In conclusion, EA could be an effective therapy to alleviated DM-induced reproductive toxicity and dysfunction in rats by a potent antioxidant potential mediated by the upregulation of Nrf2. 相似文献
92.
Fu Z Runquist JA Forouhar F Hussain M Hunt JF Miziorko HM Kim JJ 《The Journal of biological chemistry》2006,281(11):7526-7532
3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase is a key enzyme in the ketogenic pathway that supplies metabolic fuel to extrahepatic tissues. Enzyme deficiency may be due to a variety of human mutations and can be fatal. Diminished activity has been explained based on analyses of recombinant human mutant proteins or, more recently, in the context of structural models for the enzyme. We report the experimental determination of a crystal structure at 2.1 A resolution of the recombinant human mitochondrial HMG-CoA lyase containing a bound activator cation and the dicarboxylic acid 3-hydroxyglutarate. The enzyme adopts a (betaalpha)(8) barrel fold, and the N-terminal barrel end is occluded. The structure of a physiologically relevant dimer suggests that substrate access to the active site involves binding across the cavity located at the C-terminal end of the barrel. An alternative hypothesis that involves substrate insertion through a pore proposed to extend through the barrel is not compatible with the observed structure. The activator cation ligands included Asn(275), Asp(42),His(233), and His(235); the latter three residues had been implicated previously as contributing to metal binding or enzyme activity. Arg(41), previously shown to have a major effect on catalytic efficiency, is also located at the active site. In the observed structure, this residue interacts with a carboxyl group of 3-hydroxyglutarate, the hydrolysis product of the competitive inhibitor 3-hydroxyglutaryl-CoA required for crystallization of human enzyme. The structure provides a rationale for the decrease in enzyme activity due to clinical mutations, including H233R, R41Q, D42H, and D204N, that compromise active site function or enzyme stability. 相似文献
93.
Sever-Chroneos Z Krupa A Davis J Hasan M Yang CH Szeliga J Herrmann M Hussain M Geisbrecht BV Kobzik L Chroneos ZC 《The Journal of biological chemistry》2011,286(6):4854-4870
Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap(+)) but not Eap-deficient (Eap(-)) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap(+) S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly, WT mice cleared infection with Eap(+) but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap(+) S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap(-) S. aureus was impaired. Macrophages express two isoforms: SP-R210(L) and SP-R210(S). The results show that WT alveolar macrophages are distinguished by expression of SP-R210(L), whereas SR-A(-/-) alveolar macrophages are deficient in SP-R210(L) expressing only SP-R210(S). Accordingly, SR-A(-/-) mice were highly susceptible to both Eap(+) and Eap(-) S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210(L) mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A. 相似文献
94.
The self‐sufficient P450 RhF expressed in a whole cell system selectively catalyses the 5‐hydroxylation of diclofenac 下载免费PDF全文
Jan M. Klenk Bernd A. Nebel Joanne L. Porter Justyna K. Kulig Shaneela A. Hussain Sven M. Richter Michele Tavanti Nicholas J. Turner Martin A. Hayes Bernhard Hauer Sabine L. Flitsch 《Biotechnology journal》2017,12(3)
P450 monooxygenases are able to catalyze the highly regio‐ and stereoselective oxidations of many organic molecules. However, the scale‐up of such bio‐oxidations remains challenging due to the often‐low activity, level of expression and stability of P450 biocatalysts. Despite these challenges they are increasingly desirable as recombinant biocatalysts, particularly for the production of drug metabolites. Diclofenac is a widely used anti‐inflammatory drug that is persistent in the environment along with the 4'‐ and 5‐hydroxy metabolites. Here we have used the self‐sufficient P450 RhF (CYP116B2) from Rhodococcus sp. in a whole cell system to reproducibly catalyze the highly regioselective oxidation of diclofenac to 5‐hydroxydiclofenac. The product is a human metabolite and as such is an important standard for environmental and toxicological analysis. Furthermore, access to significant quantities of 5‐hydroxydiclofenac has allowed us to demonstrate further oxidative degradation to the toxic quinoneimine product. Our studies demonstrate the potential for gram‐scale production of human drug metabolites through recombinant whole cell biocatalysis. 相似文献
95.
Gibberellin (GA) is a classical plant hormone involved in many aspects of plant growth and development. A family of five homologs called the DELLA proteins, comprised of GAI, RGA, RGL1, RGL2 and RGL3, were recently found to act as critical GA signal mediators in Arabidopsis. Reports have shown that GAI and RGA are coupled together to repress stem elongation growth whereas RGL2 is a major negative regulator of seed germination. GA down-regulates DELLA proteins through protein degradation likely via the proteasome pathway. The conserved and functionally important DELLA domain is responsible for protein stability in response to GA. 相似文献
96.
Glucan, water dikinase activity stimulates breakdown of starch granules by plastidial beta-amylases 总被引:6,自引:0,他引:6 下载免费PDF全文
Edner C Li J Albrecht T Mahlow S Hejazi M Hussain H Kaplan F Guy C Smith SM Steup M Ritte G 《Plant physiology》2007,145(1):17-28
Glucan phosphorylating enzymes are required for normal mobilization of starch in leaves of Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum), but mechanisms underlying this dependency are unknown. Using two different activity assays, we aimed to identify starch degrading enzymes from Arabidopsis, whose activity is affected by glucan phosphorylation. Breakdown of granular starch by a protein fraction purified from leaf extracts increased approximately 2-fold if the granules were simultaneously phosphorylated by recombinant potato glucan, water dikinase (GWD). Using matrix-assisted laser-desorption ionization mass spectrometry several putative starch-related enzymes were identified in this fraction, among them beta-AMYLASE1 (BAM1; At3g23920) and ISOAMYLASE3 (ISA3; At4g09020). Experiments using purified recombinant enzymes showed that BAM1 activity with granules similarly increased under conditions of simultaneous starch phosphorylation. Purified recombinant potato ISA3 (StISA3) did not attack the granular starch significantly with or without glucan phosphorylation. However, starch breakdown by a mixture of BAM1 and StISA3 was 2 times higher than that by BAM1 alone and was further enhanced in the presence of GWD and ATP. Similar to BAM1, maltose release from granular starch by purified recombinant BAM3 (At4g17090), another plastid-localized beta-amylase isoform, increased 2- to 3-fold if the granules were simultaneously phosphorylated by GWD. BAM activity in turn strongly stimulated the GWD-catalyzed phosphorylation. The interdependence between the activities of GWD and BAMs offers an explanation for the severe starch excess phenotype of GWD-deficient mutants. 相似文献
97.
Formic Hydrogenlyase and the Photoassimilation of Formate by a Strain of Rhodopseudomonas palustris 总被引:1,自引:3,他引:1 下载免费PDF全文
A photosynthetic bacterium isolated by enrichment on media containing formate as major source of cell carbon was identified as a strain of Rhodopseudomonas palustris. It grew on a wide range of simple organic compounds including alcohols, fatty acids, and hydroxyacids, on a chemically defined medium with biotin and p-aminobenzoic acid as essential growth factors. The organism grew on formate or photoautotrophically with molecular hydrogen or thiosulfate only in the presence of yeast extract. Ability to photoassimilate formate could be shown only in organisms grown in the presence of formate. The organism contained an inducible formic hydrogenlyase consisting of a soluble formic dehydrogenase, a particulate hydrogenase, and one or more intermediate, but as yet unidentified, electron carriers. The formic hydrogenlyase could be reconstituted from a particulate hydrogenase and a partially purified soluble formic dehydrogenase. Some properties of the formic dehydrogenase and hydrogenase have been compared with that of the formic hydrogenlyase system. 相似文献
98.
H. Singh N. B. Singh A. Singh I. Hussain V. Yadav 《Russian Journal of Plant Physiology》2017,64(4):518-524
The present study assessed the response of pea plants exposed to herbicide induced oxidative stress in the plants present in agriculture field. We analysed the effect of exogenous nitric oxide (NO) regulated chlorophyll and protein content, nitrate reductase enzyme activity and antioxidant enzyme activity in herbicidetreated green pea (Pisum sativum L.). Glyphosate (0.25 mM) treatment alone or in combination with 250 μM sodium nitroprusside (SNP, 250 μM with glyphosate) was given to pea and we observed the changes in biophysical and biochemical parameters. During oxidative stress ion leakage is the first step of cellular damage. Supplementation of SNP with glyphosate significantly reduced ion leakage and moderately reduced H2O2 and malondialdehyde (MDA) content. SNP also increased chlorophyll content and antioxidant enzymes viz. superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (POD) activity as compared to herbicide treatment alone. The present result suggests that NO protects pea plants from damage caused by glyphosate. 相似文献
99.
Longhua Zhou Haoyi Wang Xin Chen Yuling Li Nazim Hussain Libo Cui Dezhi Wu Lixi Jiang 《Plant Growth Regulation》2017,83(3):385-396
100.