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51.
Ghantasala S Sameer Kumar Abhilash K Venugopal Anita Mahadevan Santosh Renuse H C Harsha Nandini A Sahasrabuddhe Harsh Pawar Rakesh Sharma Praveen Kumar Sudha Rajagopalan Keith Waddell Yarappa L Ramachandra Parthasarathy Satishchandra Raghothama Chaerkady T S Keshava Prasad K Shankar Akhilesh Pandey 《Clinical proteomics》2012,9(1):12
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54.
Aparna Sharma Anu Mary Varghese Kalyan Vijaylakshmi Rajendrarao Sumitha V. K. Prasanna S. Shruthi B. K. Chandrasekhar Sagar Keshava K. Datta Harsha Gowda Atchayaram Nalini Phalguni Anand Alladi Rita Christopher Talakad N. Sathyaprabha Trichur R. Raju M. M. Srinivas Bharath 《Neurochemical research》2016,41(5):965-984
In our laboratory, we have developed (1) an in vitro model of sporadic Amyotrophic Lateral Sclerosis (sALS) involving exposure of motor neurons to cerebrospinal fluid (CSF) from sALS patients and (2) an in vivo model involving intrathecal injection of sALS-CSF into rat pups. In the current study, we observed that spinal cord extract from the in vivo sALS model displayed elevated reactive oxygen species (ROS) and mitochondrial dysfunction. Quantitative proteomic analysis of sub-cellular fractions from spinal cord of the in vivo sALS model revealed down-regulation of 35 mitochondrial proteins and 4 lysosomal proteins. Many of the down-regulated mitochondrial proteins contribute to alterations in respiratory chain complexes and organellar morphology. Down-regulated lysosomal proteins Hexosaminidase, Sialidase and Aryl sulfatase also displayed lowered enzyme activity, thus validating the mass spectrometry data. Proteomic analysis and validation by western blot indicated that sALS-CSF induced the over-expression of the pro-apoptotic mitochondrial protein BNIP3L. In the in vitro model, sALS-CSF induced neurotoxicity and elevated ROS, while it lowered the mitochondrial membrane potential in rat spinal cord mitochondria in the in vivo model. Ultra structural alterations were evident in mitochondria of cultured motor neurons exposed to ALS-CSF. These observations indicate the first line evidence that sALS-CSF mediated mitochondrial and lysosomal defects collectively contribute to the pathogenesis underlying sALS. 相似文献
55.
Mutant strains in the tsaA gene encoding alkyl hydroperoxide reductase were more sensitive to O(2) and to oxidizing agents (paraquat, cumene hydroperoxide and t-butylhydroperoxide) than the wild type, but were markedly more resistant to hydrogen peroxide. The mutant strains resistance phenotype could be attributed to a 4-fold and 3-fold increase in the catalase protein amount and activity, respectively compared to the parent strain. The wild type did not show an increase in catalase expression in response to sequential increases in O(2) exposure or to oxidative stress reagents, so an adaptive compensatory mutation has probably occurred in the mutants. In support of this, chromosomal complementation of tsaA mutants restored alkyl hydroperoxide reductase, but catalase was still up-expressed in all complemented strains. The katA promoter sequence was the same in all mutant strains and the wild type. Like its Helicobacter pylori counterpart strain, a H. hepaticus tsaA mutant contained more lipid hydroperoxides than the wild type strain. Hepatic tissue from mice inoculated with a tsaA mutant had lesions similar to those inoculated with the wild type, and included coagulative necrosis of hepatocytes. The liver and cecum colonizing abilities of the wild type and tsaA mutant were comparable. Up-expression of catalase in the tsaA mutants likely permits the bacterium to compensate (in colonization and virulence attributes) for the loss of an otherwise important oxidative stress-combating enzyme, alkyl hydroperoxide reductase. The use of erythromycin resistance insertion as a facile way to screen for gene-targeted mutants, and the chromosomal complementation of those mutants are new genetic procedures for studying H. hepaticus. 相似文献
56.
Dongwei Hui Keshava N. Kumar Julie R. Mach Ashik Srinivasan Ranu Pal Xiaodong Bao Abdulbaki Agbas Georg H?fner Klaus T. Wanner Elias K. Michaelis 《The Journal of biological chemistry》2009,284(4):2245-2257
The cloning and characterization of the gene for the fourth subunit of a
glutamate-binding protein complex in rat brain synaptic membranes are
described. The cloned rat brain cDNA contained two open reading frames (ORFs)
encoding 8.9- (PRO1) and 9.5-kDa (PRO2) proteins. The cDNA sequence matched
contiguous genomic DNA sequences in rat chromosome 17. Both ORFs were
expressed within the structure of a single brain mRNA and antibodies against
unique sequences in PRO1- and PRO2-labeled brain neurons in situ,
indicative of bicistronic gene expression. Dicistronic vectors in which ORF1
and ORF2 were substituted by either two different fluorescent proteins or two
luciferases indicated concurrent, yet independent translation of the two ORFs.
Transfection with noncapped mRNA led to cap-independent translation of only
ORF2 through an internal ribosome entry sequence preceding ORF2. In
vitro or cell expression of the cloned cDNA led to the formation of
multimeric protein complexes containing both PRO1 and PRO2. These complexes
had low affinity
(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine
(MK-801)-sensitive phencyclidine-binding sites. Overexpression of PRO1 and
PRO2 in CHO cells, but not neuroblastoma cells, caused cell death within
24–48 h. The cytotoxicity was blocked by concurrent treatment with
MK-801 or by two tetrahydroisoquinolines that bind to phencyclidine sites in
neuronal membranes. Co-expression of two of the other subunits of the protein
complex together with PRO1/PRO2 abrogated the cytotoxic effect without
altering PRO1/PRO2 protein levels. Thus, this rare mammalian bicistronic gene
coded for two tightly interacting brain proteins forming a low affinity
phencyclidine-binding entity in a synaptic membrane complex.A complex of four proteins purified from brain synaptic membranes was shown
to have recognition sites for l-glutamate,
N-methyl-d-aspartate
(NMDA),4 and other
ligands characteristic of NMDA receptors in brain, including binding sites for
the co-agonist glycine, the modulator spermine, the competitive antagonist
(+)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), and the ion
channel inhibitors thienylcyclohexylpiperidine (TCP) and
(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine
(MK-801) (1,
2). Reconstitution of the
purified complex into planar lipid bilayer membranes leads to the formation of
channels with four ion conductance levels upon activation by glutamate or NMDA
in the presence of glycine (3).
These conductances differ from either the predominant NMDA-activated
receptor-ion channels of brain neurons or those formed by reconstitution of
the NMDA receptor subunits (4),
but are similar to those described for ion channels in rat spinal cord motor
neurons (5).The genes for three of the proteins in this complex have been cloned and
expressed in heterologous cells
(6–10).
The gene GRINA for the glutamate-binding protein (GBP) subunit was
identified as part of a “learning and memory” module of genes
expressed in the entorhinal cortex of the mammalian brain
(11), and as the gene
responsible for mental retardation and epilepsy in infants with a gene
duplication in chromosome 8q24.3
(12). Expression of
GRINA in heterologous cells leads to activation of mitogen-activated
protein kinases (13),
i.e. it may be involved in signal transduction in neurons. Because of
the potential role of GBP and of the associated membrane complex in cell
signaling, there is a need to fully characterize all components of the complex
and reconstitute the intact complex in cells lacking in its expression. The
genes for two other components of the complex have been cloned, those for the
glycine-binding and CPP-binding proteins. But the gene for the fourth subunit
has not yet been cloned.The fourth protein of the complex was identified on SDS-PAGE as an
∼40-kDa protein. To complete the characterization of this complex of
proteins, the cDNA for the fourth subunit was cloned, and a corresponding
genomic sequence in rat genome was identified. The presence of two open
reading frames (ORFs) in the cloned cDNA, the expression of both ORFs in a
single mRNA in brain, and the translation in brain of the two proteins coded
by the cDNA, led to the investigation of the mechanism of translation of both
ORFs. Translation of both ORFs through an internal ribosome entry sequence
(IRES) was identified, as was the need for the co-expression of the two
proteins to create a functional protein, a phencyclidine-binding protein. 相似文献
57.
58.
The Medicago FLOWERING LOCUS T homolog, MtFTa1, is a key regulator of flowering time 总被引:2,自引:0,他引:2
Laurie RE Diwadkar P Jaudal M Zhang L Hecht V Wen J Tadege M Mysore KS Putterill J Weller JL Macknight RC 《Plant physiology》2011,156(4):2207-2224
FLOWERING LOCUS T (FT) genes encode proteins that function as the mobile floral signal, florigen. In this study, we characterized five FT-like genes from the model legume, Medicago (Medicago truncatula). The different FT genes showed distinct patterns of expression and responses to environmental cues. Three of the FT genes (MtFTa1, MtFTb1, and MtFTc) were able to complement the Arabidopsis (Arabidopsis thaliana) ft-1 mutant, suggesting that they are capable of functioning as florigen. MtFTa1 is the only one of the FT genes that is up-regulated by both long days (LDs) and vernalization, conditions that promote Medicago flowering, and transgenic Medicago plants overexpressing the MtFTa1 gene flowered very rapidly. The key role MtFTa1 plays in regulating flowering was demonstrated by the identification of fta1 mutants that flowered significantly later in all conditions examined. fta1 mutants do not respond to vernalization but are still responsive to LDs, indicating that the induction of flowering by prolonged cold acts solely through MtFTa1, whereas photoperiodic induction of flowering involves other genes, possibly MtFTb1, which is only expressed in leaves under LD conditions and therefore might contribute to the photoperiodic regulation of flowering. The role of the MtFTc gene is unclear, as the ftc mutants did not have any obvious flowering-time or other phenotypes. Overall, this work reveals the diversity of the regulation and function of the Medicago FT family. 相似文献
59.
Apeksha Sahu Satwant Kumar Sreelakshmi K Sreenivasamurthy Lakshmi Dhevi N Selvan Anil K Madugundu Soujanya D Yelamanchi Vinuth N Puttamallesh Gourav Dey Abhijith K Anil Anand Srinivasan Kanchan K Mukherjee Harsha Gowda Parthasarathy Satishchandra Anita Mahadevan Akhilesh Pandey Thottethodi Subrahmanya Keshava Prasad Susarla Krishna Shankar 《Clinical proteomics》2014,11(1)
Background
Toxoplasma encephalitis is caused by the opportunistic protozoan parasite Toxoplasma gondii. Primary infection with T. gondii in immunocompetent individuals remains largely asymptomatic. In contrast, in immunocompromised individuals, reactivation of the parasite results in severe complications and mortality. Molecular changes at the protein level in the host central nervous system and proteins associated with pathogenesis of toxoplasma encephalitis are largely unexplored. We used a global quantitative proteomic strategy to identify differentially regulated proteins and affected molecular networks in the human host during T. gondii infection with HIV co-infection.Results
We identified 3,496 proteins out of which 607 proteins were differentially expressed (≥1.5-fold) when frontal lobe of the brain from patients diagnosed with toxoplasma encephalitis was compared to control brain tissues. We validated differential expression of 3 proteins through immunohistochemistry, which was confirmed to be consistent with mass spectrometry analysis. Pathway analysis of differentially expressed proteins indicated deregulation of several pathways involved in antigen processing, immune response, neuronal growth, neurotransmitter transport and energy metabolism.Conclusions
Global quantitative proteomic approach adopted in this study generated a comparative proteome profile of brain tissues from toxoplasma encephalitis patients co-infected with HIV. Differentially expressed proteins include previously reported and several new proteins in the context of T. gondii and HIV infection, which can be further investigated. Molecular pathways identified to be associated with the disease should enhance our understanding of pathogenesis in toxoplasma encephalitis.Electronic supplementary material
The online version of this article (doi:10.1186/1559-0275-11-39) contains supplementary material, which is available to authorized users. 相似文献60.
Waheed Arshad Ihsan-ul- Haq Mohammad Tahir Waheed Kirankumar S. Mysore Bushra Mirza 《PloS one》2014,9(5)
Tomato (Solanum lycopersicum L.) is the second most important cultivated crop next to potato, worldwide. Tomato serves as an important source of antioxidants in human diet. Alternaria solani and Fusarium oxysporum cause early blight and vascular wilt of tomato, respectively, resulting in severe crop losses. The foremost objective of the present study was to generate transgenic tomato plants with rolB gene and evaluate its effect on plant morphology, nutritional contents, yield and resistance against fungal infection. Tomato cv. Rio Grande was transformed via Agrobacterium tumefaciens harbouring rolB gene of Agrobacterium rhizogenes. rolB. Biochemical analyses showed considerable improvement in nutritional quality of transgenic tomato fruits as indicated by 62% increase in lycopene content, 225% in ascorbic acid content, 58% in total phenolics and 26% in free radical scavenging activity. Furthermore, rolB gene significantly improved the defence response of leaves of transgenic plants against two pathogenic fungal strains A. solani and F. oxysporum. Contrarily, transformed plants exhibited altered morphology and reduced fruit yield. In conclusion, rolB gene from A. rhizogenes can be used to generate transgenic tomato with increased nutritional contents of fruits as well as improved foliar tolerance against fungal pathogens. 相似文献