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101.
Rais Ahmad Khan Hamad A. Al-Lohedan Mohammad Abul Farah Mohd Sajid Ali Ali Alsalme Khalid Mashay Al-Anazi 《Journal of biomolecular structure & dynamics》2013,31(15):3905-3913
abstractThe designing of metal-based anticancer therapeutic agents can be optimized in a better and rapid way if the ligands utilized have standalone properties. Therefore, even when the organometallic/coordination complex (i.e., metallodrug) gets dissociated in extreme conditions, the ligand can endorse its biological properties. Herein, we have synthesized and characterized ?6-p-cymene ruthenium diclofenac complex. Furthermore, the ruthenium complex interactions with human serum albumin (HSA) and ct-DNA have been studied using various spectroscopic studies viz., UV, fluorescence, and circular dichroism and exhibited a significant binding propensity. Furthermore, in vitro cytotoxicity assays were carried out against human breast cancer “MCF-7” cell line. The ?6-p-cymene ruthenium diclofenac complex registered significant cytotoxicity with an IC50 value of ~25.0?µM which is comparable to the standard drugs. The ?6-p-cymene ruthenium diclofenac complex was able to decrease the MCF-7 cell proliferation and induced significant levels of apoptosis with relatively low toxicity. 相似文献
102.
Masrina Mohd Nadzir Masahiro Kino-oka Katsura Sugawara Masahito Taya 《Biotechnology letters》2013,35(2):295-300
The effect of insulin-like growth factor-1 (IGF-1) on the behavior of rabbit chondrocytes in cultured collagen (CL) gels initially seeded with 2 × 105 cells/ml was examined. On day 5, the frequency of migrating cells cultured in presence of 100 ng IGF-1/ml was 0.04, which was 54 % of the frequency in IGF-1-free culture. The presence of IGF-1 caused an increase in the frequency of dividing cells from 0.09 to 0.13. These results suggest that IGF-1 suppressed the migration of chondrocytes in the CL gels while stimulating cell division in the initial culture phase. The proteolytic migration of cells was thought to be suppressed by the down-regulation of membrane type 1 matrix metalloproteinase by IGF-1. This contributed to the formation of aggregates with spherical-shaped cells that produced collagen type II. 相似文献
103.
M. Iqbal Hossain Carli L. Roulston M. Aizuddin Kamaruddin Percy W. Y. Chu Dominic C. H. Ng Gregory J. Dusting Jeffrey D. Bjorge Nicholas A. Williamson Donald J. Fujita Steve N. Cheung Tung O. Chan Andrew F. Hill Heung-Chin Cheng 《The Journal of biological chemistry》2013,288(14):9696-9709
Excitotoxicity resulting from overstimulation of glutamate receptors is a major cause of neuronal death in cerebral ischemic stroke. The overstimulated ionotropic glutamate receptors exert their neurotoxic effects in part by overactivation of calpains, which induce neuronal death by catalyzing limited proteolysis of specific cellular proteins. Here, we report that in cultured cortical neurons and in vivo in a rat model of focal ischemic stroke, the tyrosine kinase Src is cleaved by calpains at a site in the N-terminal unique domain. This generates a truncated Src fragment of ∼52 kDa, which we localized predominantly to the cytosol. A cell membrane-permeable fusion peptide derived from the unique domain of Src prevents calpain from cleaving Src in neurons and protects against excitotoxic neuronal death. To explore the role of the truncated Src fragment in neuronal death, we expressed a recombinant truncated Src fragment in cultured neurons and examined how it affects neuronal survival. Expression of this fragment, which lacks the myristoylation motif and unique domain, was sufficient to induce neuronal death. Furthermore, inactivation of the prosurvival kinase Akt is a key step in its neurotoxic signaling pathway. Because Src maintains neuronal survival, our results implicate calpain cleavage as a molecular switch converting Src from a promoter of cell survival to a mediator of neuronal death in excitotoxicity. Besides unveiling a new pathological action of Src, our discovery of the neurotoxic action of the truncated Src fragment suggests new therapeutic strategies with the potential to minimize brain damage in ischemic stroke. 相似文献
104.
Gustavo Basurto-Islas Inge Grundke-Iqbal Yunn Chyn Tung Fei Liu Khalid Iqbal 《The Journal of biological chemistry》2013,288(24):17495-17507
Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I2PP2A. In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2PP2A is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2PP2A translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2PP2A, except when I2PP2A was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2PP2A, inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2PP2A-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target. 相似文献
105.
Syed Ghulam Musharraf Arslan Ali Naik Tameem Khan Maria Yousuf Muhammad Iqbal Choudhary 《Steroids》2013,78(2):171-181
Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to investigate the effect of different substitutions introduced during metabolism on fragmentation patterns of four anabolic steroids including methyltestosterone, methandrostenolone, cis-androsterone and adrenosterone, along with their metabolites. Collision-induced dissociation (CID) analysis was performed to correlate the major product ions of 19 steroids with structural features. The analysis is done to portray metabolic alteration, such as incorporation or reduction of double bonds, hydroxylations, and/or oxidation of hydroxyl moieties to keto functional group on steroidal skeleton which leads to drastically changed product ion spectra from the respective classes of steroids, therefore, making them difficult to identify. The comparative ESI-MS/MS study also revealed some characteristic peaks to differentiate different steroidal metabolites and can be useful for the unambiguous identification of anabolic steroids in biological fluid. Moreover, LC–ESI-MS/MS analysis of fermented extract of methyltestosterone, obtained by Macrophomina phaseolina was also investigated. 相似文献
106.
107.
Dang Lelamurni Abd Razak Noorlidah Abdullah Norjuliza Mohd Khir Johari Vikineswary Sabaratnam 《Applied microbiology and biotechnology》2013,97(7):3207-3213
The potential for using agricultural and industrial by-products as substrate for the production of the edible mushroom, Auricularia polytricha, was evaluated using several formulations of selected palm oil wastes mixed with sawdust and further supplemented with selected nitrogen sources. The best substrate formulations were sawdust (SD) mixed with oil palm frond (OPF; 90:10) added with 15 % spent grain (SG) and sawdust mixed with empty fruit bunch (EFB; 50:50) added with 10 % spent grain (SG) with mycelia growth rate of 8 mm/day and 7 mm/day respectively. These two substrate formulations were then subjected to different moisture content levels (65 %, 75 % and 85 %). Highest total fresh sporophore yield at 0.43 % was obtained on SD?+?OPF (90:10)?+?15 % SG at 85 % moisture content, followed closely by SD?+?EFB (50:50)?+?10 % SG with 0.40 % total yield, also at 85 % moisture content. Each of the substrate formulations at 85 % moisture content gave the highest biological efficiency (BE) at 288.9 % and 260.7 %, respectively. Both yield and biological efficiency of A. polytricha on these two formulations were almost three times higher when compared to sawdust substrate alone, thus proving the potential of these formulations to improve yield of this mushroom. 相似文献
108.
Md. Ejaz Ahmed Mohd. Moshahid Khan Hayate Javed Kumar Vaibhav Andleeb Khan Rizwana Tabassum Mohammad Ashafaq Farah Islam Mohammed M. Safhi Fakhrul Islam 《Neurochemistry international》2013
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline and enhancement of oxidative loads in the brain. Flavonoids have been considered to exert human health benefits by anti-oxidant and anti-inflammatory properties. The present study is aimed to elucidate the neuroprotective effect of catechin hydrate (CH), a natural flavanoid with potential antioxidant and anti-inflammatory properties, on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were pretreated with CH (10 and 20 mg/kg bwt) orally once daily for 21 days and then bilaterally injected with ICV-STZ (3 mg/kg bwt), while sham group rats receive the same volume of vehicle. After 2 weeks of ICV-STZ infusion, rats were tested for cognitive performance using Morris water maze (MWM) test and then sacrifice for biochemical and histopathological assays. CH was found to be successful in upregulating the antioxidant status and prevented the memory loss. The expression of choline acetyl transferase (ChAT) was decreased in ICV-STZ group and CH pretreatment increases the expression of ChAT. Moreover, inflammatory mediators like TNF-α, IL-1β levels and expression of iNOS were significantly attenuated by CH pretreatment. The study suggests that CH is effective in preventing memory loss, ameliorating the oxidative stress and might be beneficial for the treatment of sporadic dementia of Alzheimer’s type (SDAT). 相似文献
109.
Emrah Celik Mohd.?Hafeez Faridi Vinay Kumar Shashank Deep Vincent?T. Moy Vineet Gupta 《Biophysical journal》2013,105(11):2517-2527
Integrin CD11b/CD18 is a key adhesion receptor that mediates leukocyte migration and immune functions. Leukadherin-1 (LA1) is a small molecule agonist that enhances CD11b/CD18-dependent cell adhesion to its ligand ICAM-1. Here, we used single-molecule force spectroscopy to investigate the biophysical mechanism by which LA1-activated CD11b/CD18 mediates leukocyte adhesion. Between the two distinct populations of CD11b/CD18:ICAM-1 complex that participate in cell adhesion, the cytoskeleton(CSK)-anchored elastic elements and the membrane tethers, we found that LA1 enhanced binding of CD11b/CD18 on K562 cells to ICAM-1 via the formation of long membrane tethers, whereas Mn2+ additionally increased ICAM-1 binding via CSK-anchored bonds. LA1 activated wild-type and LFA1−/− neutrophils also showed longer detachment distances and time from ICAM-1-coated atomic force microscopy tips, but significantly lower detachment force, as compared to the Mn2+-activated cells, confirming that LA1 primarily increased membrane-tether bonds to enhance CD11b/CD18:ICAM-1 binding, whereas Mn2+ induced additional CSK-anchored bond formation. The results suggest that the two types of agonists differentially activate integrins and couple them to the cellular machinery, providing what we feel are new insights into signal mechanotransduction by such agents. 相似文献
110.
Mohd Zulkhairi Mohd Yusoff Yuya Hashiguchi Toshinari Maeda Thomas K. Wood 《Biochemical and biophysical research communications》2013
Pseudogenes are considered to be nonfunctional genes that lack a physiological role. By screening 3985 Escherichia coli mutants using chemochromic membranes, we found four pseudogenes involved in hydrogen metabolism. Knockouts of pseudogenes ydfW and ypdJ had a defective hydrogen phenotype on glucose and formate, respectively. Also, the knockout of pseudogene yqiG formed hydrogen from formate but not from glucose. For the yqiG mutant, 100% hydrogen recovery was obtained by the complementation of YqiG via a plasmid. The knockout of pseudogene ylcE showed hydrogen deficiency in minimal media which suggested that the role of YlcE is associated with cell growth. Hence, the products of these four pseudogenes play an important physiological role in hydrogen production in E. coli. 相似文献