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91.
Michael P. Kurnellas Sara E. Brownell Leon Su Andrey V. Malkovskiy Jayakumar Rajadas Gregory Dolganov Sidharth Chopra Gary K. Schoolnik Raymond A. Sobel Jonathan Webster Shalina S. Ousman Rachel A. Becker Lawrence Steinman Jonathan B. Rothbard 《The Journal of biological chemistry》2012,287(43):36423-36434
To determine whether the therapeutic activity of αB crystallin, small heat shock protein B5 (HspB5), was shared with other human sHsps, a set of seven human family members, a mutant of HspB5 G120 known to exhibit reduced chaperone activity, and a mycobacterial sHsp were expressed and purified from bacteria. Each of the recombinant proteins was shown to be a functional chaperone, capable of inhibiting aggregation of denatured insulin with varying efficiency. When injected into mice at the peak of disease, they were all effective in reducing the paralysis in experimental autoimmune encephalomyelitis. Additional structure activity correlations between chaperone activity and therapeutic function were established when linear regions within HspB5 were examined. A single region, corresponding to residues 73–92 of HspB5, forms amyloid fibrils, exhibited chaperone activity, and was an effective therapeutic for encephalomyelitis. The linkage of the three activities was further established by demonstrating individual substitutions of critical hydrophobic amino acids in the peptide resulted in the loss of all of the functions. 相似文献
92.
J Jerobin RS Sureshkumar CH Anjali A Mukherjee N Chandrasekaran 《Carbohydrate polymers》2012,90(4):1750-1756
Azadirachtin a biological compound found in neem have medicinal and pesticidal properties. The present work reports on the encapsulation of neem oil nanoemulsion using sodium alginate (Na-Alg) by cross linking with glutaraldehyde. Starch and polyethylene glycol (PEG) were used as coating agents for smooth surface of beads. The SEM images showed beads exhibited nearly spherical shape. Swelling of the polymeric beads reduced with coating which in turn decreased the rate of release of Aza-A. Starch coated encapsulation of neem oil nanoemulsion was found to be effective when compared to PEG coated encapsulation of neem oil nanoemulsion. The release rate of neem Aza-A from the beads into an aqueous environment was analyzed by UV-visible spectrophotometer (214nm). The encapsulated neem oil nanoemulsion have the potential for controlled release of Aza-A. Neem oil nanoemulsion encapsulated beads coated with PEG was found to be toxic in lymphocyte cells. 相似文献
93.
R. Jayakumar Amrita NairN. Sanoj Rejinold S. MayaS.V. Nair 《Carbohydrate polymers》2012,87(3):2352-2356
This work deals with preparation of doxorubicin loaded chitin nanogels and were characterized by SEM, DLS and FTIR for cancer drug delivery. The in vitro cytotoxicity studies of 130-160 nm sized doxorubicin loaded chitin nanogels were studied using MTT assay on L929, PC3, MCF-7, A549 and HEPG2 confirmed that relatively higher toxicity on cancer cells comparing to normal L929 cells. The internalization studies showed a significant uptake of doxorubicin loaded chitin nanogels in all the tested cell lines. All the above results indicated that doxorubicin loaded chitin nanogels can be used for prostate, breast, lung and liver cancer. 相似文献
94.
Amirtharaj GJ Natarajan SK Mukhopadhya A Zachariah UG Hegde SK Kurian G Balasubramanian KA Ramachandran A 《Biochimica et biophysica acta》2008,1782(5):349-354
Human serum albumin binds ligands such as fatty acids and metals in circulation. Oxidative stress can modify albumin and affect ligand binding. This study examines the role of oxidative stress and fatty acids in modulating cobalt binding to albumin in patients with fatty liver. Elevated levels of malondialdehyde and protein carbonyls, indicative of oxidative stress were evident in serum of patients with fatty liver. A significant decrease in albumin-cobalt binding was also observed. Albumin isolated from patient serum also showed an increase in bound fatty acids. In vitro experiments indicated that while oxidant exposure or removal of fatty acids independently decreased cobalt binding to albumin, removal of fatty acids from the protein prior to oxidant exposure did not influence the oxidant effect on albumin-cobalt binding. These results suggest that oxidative stress and fatty acids on albumin can influence albumin-cobalt binding in patients with fatty liver by independent mechanisms. 相似文献
95.
Jayakumar AR Liu M Moriyama M Ramakrishnan R Forbush B Reddy PV Norenberg MD 《The Journal of biological chemistry》2008,283(49):33874-33882
Brain edema and the consequent increase in intracranial pressure and brain herniation are major complications of acute liver failure (fulminant hepatic failure) and a major cause of death in this condition. Ammonia has been strongly implicated as an important factor, and astrocyte swelling appears to be primarily responsible for the edema. Ammonia is known to cause cell swelling in cultured astrocytes, although the means by which this occurs has not been fully elucidated. A disturbance in one or more of these systems may result in loss of ion homeostasis and cell swelling. In particular, activation of the Na-K-Cl cotransporter (NKCC1) has been shown to be involved in cell swelling in several neurological disorders. We therefore examined the effect of ammonia on NKCC activity and its potential role in the swelling of astrocytes. Cultured astrocytes were exposed to ammonia (NH(4)Cl; 5 mm), and NKCC activity was measured. Ammonia increased NKCC activity at 24 h. Inhibition of this activity by bumetanide diminished ammonia-induced astrocyte swelling. Ammonia also increased total as well as phosphorylated NKCC1. Treatment with cyclohexamide, a potent inhibitor of protein synthesis, diminished NKCC1 protein expression and NKCC activity. Since ammonia is known to induce oxidative/nitrosative stress, and antioxidants and nitric-oxide synthase inhibition diminish astrocyte swelling, we also examined whether ammonia caused oxidation and/or nitration of NKCC1. Cultures exposed to ammonia increased the state of oxidation and nitration of NKCC1, whereas the antioxidants N-nitro-l-arginine methyl ester and uric acid all significantly diminished NKCC activity. These agents also reduced phosphorylated NKCC1 expression. These results suggest that activation of NKCC1 is an important factor in the mediation of astrocyte swelling by ammonia and that such activation appears to be mediated by NKCC1 abundance as well as by its oxidation/nitration and phosphorylation. 相似文献
96.
Jesudason EP Masilamoni JG Jebaraj CE Paul SF Jayakumar R 《Molecular and cellular biochemistry》2008,313(1-2):113-123
Inflammation can activate macrophages or monocytes and sequentially release several inflammatory cytokines and reactive oxygen species (ROS). Oxidative stress-induced acute inflammatory response plays an important role in several diseases. This study was designed to investigate the prophylactic effect of the antioxidant lipoic acid (LA) during inflammation-induced mice. Mice were divided in to three groups (n = 8 in each): control, systemic inflammation, and LA treated mice with systemic inflammation. Results show that ROS was significantly higher in lymphocytes, hepatocytes, and astrocytes (P < 0.05) of inflammation induced mice when compared with control but no significant changes were observed in the LA treated group. Increased levels of lipid peroxidation (LPO) and decreased activities of oxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione, and ATPase were observed in the inflammation-induced mice, which returned to near normalcy following LA therapy. In vitro study has shown that LA treatment not only suppresses the increased LPO levels but also inhibits the lipid break down resulting from autoxidation. In addition, increased immunoreactivity of the astrocyte marker glial fibrillary acidic protein (GFAP) was observed in the neocortex region of inflammation-induced mice, whereas nuclear factor kappa B p65 (NFkappaB) immunoreactivity was observed in both the neocortex and liver of the same group which were effectively controlled by LA therapy suggesting that LA can efficiently manage systemic inflammation. 相似文献
97.
Masilamoni JG Jesudason EP Dhandayuthapani S Ashok BS Vignesh S Jebaraj WC Paul SF Jayakumar R 《Free radical research》2008,42(7):661-673
Widespread cerebral deposition of a 40-42 amino acid peptide called amyloid beta peptide (A beta) in the form of amyloid fibrils is one of the most prominent neuropathologic features of Alzheimer's disease (AD). The clinical study provides evidence that accumulation of protofibrils due to the Arctic mutation (E22G) causes early AD onset. Melatonin showed beneficial effects in an AD mouse model. Mice were divided into four different groups (n=8 per group): (i) control group, (ii) scrambled A beta-injected group, (iii) A beta protofibril-injected group and (iv) melatonin-treated group. A single dose of (5 microg) A beta protofibril was administered to the A beta protofibril-injected and melatonin-treated groups via intracerebroventricular injections. The results demonstrate that melatonin treatment significantly reduces A beta protofibril-induced reactive oxygen species (ROS) production, intracellular calcium levels and acetylcholinesterase activity in the neocortex and hippocampus regions. Based on these findings it is suggested that melatonin therapy might be a useful treatment for AD patients. 相似文献
98.
Synthesis, characterization and bioactivity studies of novel beta-chitin scaffolds for tissue-engineering applications 总被引:1,自引:0,他引:1
Maeda Y Jayakumar R Nagahama H Furuike T Tamura H 《International journal of biological macromolecules》2008,42(5):463-467
Chitin is a biopolymer and it is non-toxic, biodegradable and biocompatible. Chitin has many potential industrial applications because of its abundance, biodegradability, non-toxicity, chemical inertness. beta-Chitin scaffolds were prepared by using saturated calcium chloride alcoholic solution (CaCl(2).6H(2)O/EtOH) and then followed by dialysis with lyophilization. The prepared beta-chitin scaffolds were characterized by FT-IR, scanning electron microscopy (SEM) and thermogravimetric (TGA). The preliminary bioactivity studies of beta-chitin scaffolds were studied by using simulated body fluid (SBF) solution for 7, 14 and 21 days. We also immersed the beta-chitin scaffolds in saturated aqueous CaCl(2) and Na(2)HPO(4) solution over 12h. After 7, 14 and 21 days, the scaffolds were characterized by SEM and FT-IR studies. The SEM studies showed that there is a calcium phosphate layer in the surface as well as in the cross-section of beta-chitin scaffolds. It seems that the beta-chitin scaffolds are useful in the tissue-engineering field. 相似文献
99.
Jayakumar R Selvamurugan N Nair SV Tokura S Tamura H 《International journal of biological macromolecules》2008,43(3):221-225
Biomaterials such as chitin, chitosan and their derivatives have a significant and rapid development in recent years. Chitin and chitosan have become cynosure of all party because of an unusual combination of biological activities plus mechanical and physical properties. However, the applications of chitin and chitosan are limited due to its insolubility in most of the solvents. The chemical modification of chitin and chitosan are keen interest because of these modifications would not change the fundamental skeleton of chitin and chitosan but would keep the original physicochemical and biochemical properties. They would also bring new or improved properties. The chemical modification of chitin and chitosan by phosphorylation is expected to be biocompatible and is able to promote tissue regeneration. In view of rapidly growing interest in chitin and chitosan and their chemical modified derivatives, we are here focusing the recent developments on preparation of phosphorylated chitin and chitosan in different methods. 相似文献
100.
Yang T Knowles JK Lu Q Zhang H Arancio O Moore LA Chang T Wang Q Andreasson K Rajadas J Fuller GG Xie Y Massa SM Longo FM 《PloS one》2008,3(11):e3604
The p75 neurotrophin receptor (p75(NTR)) is expressed by neurons particularly vulnerable in Alzheimer's disease (AD). We tested the hypothesis that non-peptide, small molecule p75(NTR) ligands found to promote survival signaling might prevent Abeta-induced degeneration and synaptic dysfunction. These ligands inhibited Abeta-induced neuritic dystrophy, death of cultured neurons and Abeta-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Abeta-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3beta and c-Jun, and tau phosphorylation, and prevented Abeta-induced inactivation of AKT and CREB. Finally, a p75(NTR) ligand blocked Abeta-induced hippocampal LTP impairment. These studies support an extensive intersection between p75(NTR) signaling and Abeta pathogenic mechanisms, and introduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling pathways, reverse synaptic impairment and inhibit Abeta-induced neuronal dystrophy and death. 相似文献