Acetylcholinesterase [AChE] activity and isozyme pattern in normal and lithium-treated developing chick brain

Literature Survey: - Acetylcholinesterase [AChE] is an enzyme that terminates Acetylcholine [ACh] mediated neurotransmission. Its wide neuronal and non-neuronal cellular distribution has made it the focus of intense research. The data on tissue and species specific AChE expression, the detection of its various isoforms and its cholinergic and non-cholinergic functions has been accumulated and reviewed from a range of evolutionary diverse vertebrates and invertebrates that include insects, nematodes, fish, reptiles, birds and several mammals, among them man. Project Work: - Acetylcholinesterase [AChE], the lytic enzyme of the cholinergic system, functions in hydrolyzing the neurotransmitter Acetylcholine [ACh] and hence is used as a marker for cholinergic function. In vertebrates the protein is synthesized by a single gene and undergoes alternative splicing to give several isoforms. This enzyme and its isoforms are also involved in synaptogenesis, modulated by stages of development and differentially distributed in the brain. Not only is it known to be a marker for the developing chick brain, but is also implicated in neurodegenerative diseases like Alzheimer’s Disease. Isozyme Pattern of AChE is suggested to serve as a useful prognostic marker in neuronal degeneration. Lithium, a well-known teratogen, has been shown in our laboratory to induce apoptosis in a developing chick brain. Understanding the dynamics of AChE isoform pattern in lithium induced neural tissue damage would help elucidating the role of these isoforms in a degenerating system and add to our understanding of neurodegenerative diseases. We have therefore studied activity and isozyme pattern of AChE in lithium-treated and control 7-day old developing chick brain and report the same

Effect of lithium on acetylcholine esterase activity, and isozyme pattern in developing chick brain

Acetylcholine Esterase is an enzyme, which hydrolyses acetylcholine and is used as a marker for cholinergic neural function. It is known to be involved in synaptogenesis. While on one hand it is known to be a marker for the developing chick brain it is also implicated in neurodegenerative diseases. In vertebrates the protein is synthesized by a single gene and undergoes alternative splicing to give 6-8 isoforms. Isozyme patterns of acetylcholine esterase have been suggested to be useful prognostic markers of neuronal degeneration. Lithium a well-known teratogen is known to induce apoptosis in the developing chick brain. Understanding the dynamics of acetylcholine esterase isoform pattern in lithium induced neural tissue damage would help elucidating the role of these isoforms in frank neurodegenerative diseases. We have therefore studied activity and isozyme pattern of acetylcholine esterase in lithium treated and control 7 day old developing chick brain and report the same

A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo

BACKGROUND: In search of a suitable GSH-depleting agent, a novel copper complex viz., copper N-(2-hydroxyacetophenone) glycinate (CuNG) has been synthesized, which was initially found to be a potential resistance modifying agent and later found to be an immunomodulator in mice model in different doses. The objective of the present work was to decipher the effect of CuNG on reactive oxygen species (ROS) generation and antioxidant enzymes in normal and doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)-bearing Swiss albino mice. METHODS: The effect of CuNG has been studied on ROS generation, multidrug resistance-associated protein1 (MRP1) expression and on activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). RESULTS: CuNG increased ROS generation and reduced MRP1 expression in EAC/Dox cells while only temporarily depleted glutathione (GSH) within 2 h in heart, kidney, liver and lung of EAC/Dox bearing mice, which were restored within 24 h. The level of liver Cu was observed to be inversely proportional to the level of GSH. Moreover, CuNG modulated SOD, CAT and GPx in different organs and thereby reduced oxidative stress. Thus nontoxic dose of CuNG may be utilized to reduce MRP1 expression and thus sensitize EAC/Dox cells to standard chemotherapy. Moreover, CuNG modulated SOD, CAT and and GPx activities to reduce oxidative stress in some vital organs of EAC/Dox bearing mice. CuNG treatment also helped to recover liver and renal function in EAC/Dox bearing mice. CONCLUSION: Based on our studies, we conclude that CuNG may be a promising candidate to sensitize drug resistant cancers in the clinic

Functional and Molecular Effects of Arginine Butyrate and Prednisone on Muscle and Heart in the mdx Mouse Model of Duchenne Muscular Dystrophy

The number of promising therapeutic interventions for Duchenne Muscular Dystrophy (DMD) is increasing rapidly. One of the proposed strategies is to use drugs that are known to act by multiple different mechanisms including inducing of homologous fetal form of adult genes, for example utrophin in place of dystrophin.In this study, we have treated mdx mice with arginine butyrate, prednisone, or a combination of arginine butyrate and prednisone for 6 months, beginning at 3 months of age, and have comprehensively evaluated the functional, biochemical, histological, and molecular effects of the treatments in this DMD model. Arginine butyrate treatment improved grip strength and decreased fibrosis in the gastrocnemius muscle, but did not produce significant improvement in muscle and cardiac histology, heart function, behavioral measurements, or serum creatine kinase levels. In contrast, 6 months of chronic continuous prednisone treatment resulted in deterioration in functional, histological, and biochemical measures. Arginine butyrate-treated mice gene expression profiling experiments revealed that several genes that control cell proliferation, growth and differentiation are differentially expressed consistent with its histone deacetylase inhibitory activity when compared to control (saline-treated) mdx mice. Prednisone and combination treated groups showed alterations in the expression of genes that control fibrosis, inflammation, myogenesis and atrophy.These data indicate that 6 months treatment with arginine butyrate can produce modest beneficial effects on dystrophic pathology in mdx mice by reducing fibrosis and promoting muscle function while chronic continuous treatment with prednisone showed deleterious effects to skeletal and cardiac muscle. Our results clearly indicate the usefulness of multiple assays systems to monitor both beneficial and toxic effects of drugs with broad range of in vivo activity

Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence

Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the development of gliomas and other human malignancies. Mutant IDH1 induces epigenetic changes that promote tumorigenesis, but the scale and reversibility of these changes are unknown. Here, using human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic reprogramming. We characterize the reversibility of the alterations in DNA methylation, the histone landscape, and transcriptional reprogramming that occur following IDH1 mutation. We discover genome-wide coordinate changes in the localization and intensity of multiple histone marks and chromatin states. Mutant IDH1 establishes a CD24+ population with a proliferative advantage and stem-like transcriptional features. Strikingly, prolonged exposure to mutant IDH1 results in irreversible genomic and epigenetic alterations. Together, these observations provide unprecedented high-resolution molecular portraits of mutant-IDH1-dependent epigenomic reprogramming. These findings have substantial implications for understanding of mutant IDH function and for optimizing therapeutic approaches to targeting IDH-mutant tumors

Not Available

Not AvailableImproved-Samba-Mahsuri (ISM), a high-yielding, popular bacterial blight resistant (possessing Xa21, xa13, and xa5), fne-grain type, low glycemic index rice variety is highly sensitive to low soil phosphorus (P). We have deployed marker-assisted backcross breeding (MABB) approach for targeted transfer of Pup1, a major QTL associated with low soil P tolerance, using Swarna as a donor. A new co-dominant marker, K20-1-1, which is specifc for Pup1 was designed and used for foreground selection along with functional markers specifc for the bacterial blight resistance genes, Xa21, xa13, and xa5. A set of 66 polymorphic SSR marker were used for the background selection along with a pair of fanking markers for the recombination selection in backcross derived progenies and in BC2F2 generation, 12 plants, which are homozygous for Pup1, all the three bacterial blight resistance genes and possessing agro-morphological traits equivalent to or better than ISM were selected and selfed to produce BC2F3s. They were evaluated in plots with low soil P and normal soil P at ICARIIRR, Hyderabad for their low soil P tolerance, and bacterial blight resistance and superior lines were advanced to BC2F6. One of the lines, when tested at multiple locations in India was found promising under both normal as well as low soil P conditions.Not Availabl