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101.
Autophagy is a catabolic process in which lysosomes degrade intracytoplasmic contents transported in double-membraned autophagosomes. Autophagosomes are formed by the elongation and fusion of phagophores, which can be derived from preautophagosomal structures coming from the plasma membrane and other sites like the endoplasmic reticulum and mitochondria. The mechanisms by which preautophagosomal structures elongate their membranes and mature toward fully formed autophagosomes still remain unknown. Here, we show that the maturation of the early Atg16L1 precursors requires homotypic fusion, which is essential for subsequent autophagosome formation. Atg16L1 precursor homotypic fusion depends on the SNARE protein VAMP7 together with partner SNAREs. Atg16L1 precursor homotypic fusion is a critical event in the early phases of autophagy that couples membrane acquisition and autophagosome biogenesis, as this step regulates the size of the vesicles, which in turn appears to influence their subsequent maturation into LC3-positive autophagosomes. 相似文献
102.
Mancuso DJ Han X Jenkins CM Lehman JJ Sambandam N Sims HF Yang J Yan W Yang K Green K Abendschein DR Saffitz JE Gross RW 《The Journal of biological chemistry》2007,282(12):9216-9227
Previously, we identified calcium-independent phospholipase A2gamma (iPLA2gamma) with multiple translation initiation sites and dual mitochondrial and peroxisomal localization motifs. To determine the role of iPLA2gamma in integrating lipid and energy metabolism, we generated transgenic mice containing the alpha-myosin heavy chain promoter (alphaMHC) placed proximally to the human iPLA2gamma coding sequence that resulted in cardiac myocyte-restricted expression of iPLA2gamma (TGiPLA2gamma). TGiPLA2gamma mice possessed multiple phenotypes including: 1) a dramatic approximately 35% reduction in myocardial phospholipid mass in both the fed and mildly fasted states; 2) a marked accumulation of triglycerides during brief caloric restriction that represented 50% of total myocardial lipid mass; and 3) acute fasting-induced hemodynamic dysfunction. Biochemical characterization of the TGiPLA2gamma protein expressed in cardiac myocytes demonstrated over 25 distinct isoforms by two-dimensional SDS-PAGE Western analysis. Immunohistochemistry identified iPLA2gamma in the peroxisomal and mitochondrial compartments in both wild type and transgenic myocardium. Electron microscopy revealed the presence of loosely packed and disorganized mitochondrial cristae in TGiPLA2gamma mice that were accompanied by defects in mitochondrial function. Moreover, markedly elevated levels of 1-hydroxyl-2-arachidonoyl-sn-glycero-3-phosphocholine and 1-hydroxyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine were prominent in the TGiPLA2gamma myocardium identifying the production of signaling metabolites by this enzyme in vivo. Collectively, these results identified the participation of iPLA2gamma in the remarkable lipid plasticity of myocardium, its role in generating signaling metabolites, and its prominent effects in modulating energy storage and utilization in myocardium in different metabolic contexts. 相似文献
103.
Ravikumar RL Patil BS Soregaon CD Hegde SG 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2007,114(4):619-625
Gametophytic selection can drastically reduce the number of selection cycles during crop improvement programs. The objective
of the present investigation was to test whether the nature of inheritance of two unlinked disease-resistant loci, h
1 and h
2, against Fusarium wilt in chickpea (Cicer arietinum L.) under gametophytic (pollen) selection was similar to that already observed at sporophytic level. A homozygous dominant
(H
1
H
1
H
2
H
2) susceptible genotype JG-62 was crossed to a recessive (h
1
h
1
h
2
h
2) resistant genotype WR-315 to produce 20 F1 hybrid seeds. In the following generation, flower buds of 10 F1 hybrid plants were subjected to toxin stress before anthesis and the remaining ten control F1 plants’ flowers were sprayed with water. Thirty-four selected BC1 plants were generated by test crossing resistant WR-315 individuals with pollen from toxin-stressed F1 individuals. Both control and treated F1 plants were selfed to produce respective F2 generations. Two DNA markers, CS-27700bp and A07C430bp, linked to susceptible alleles H
1 and H
2, respectively, were used to study the inheritance patterns of h
1 and h
2 loci in the F2 and BC1 generations. One hundred and forty-four selected F2, 129 control F2, and 34 selected backcross individuals were tested for the presence or absence of DNA markers. Except for the control F2, observed ratios of selected F2 and BC1 populations exhibited significant chi-square deviations from expected monogenic and digenic ratios. Our results suggest that
gametophytic selection is as effective as that realized at the sporophytic level, and that the gametophytic selection can
be an effective breeding tool for plant breeding programs. 相似文献
104.
Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells 总被引:2,自引:0,他引:2
Deng H Makizumi R Ravikumar TS Dong H Yang W Yang WL 《Experimental cell research》2007,313(5):1033-1044
Bone morphogenetic protein (BMP), a member of the TGF-beta superfamily, is involved in development, morphogenesis, cell proliferation and apoptosis. Dysregulation of BMP signaling has been suggested in tumorigenesis. In an analysis of human colon normal mucosa and tumors at different stages by immunohistochemistry, we observed that the intensity of BMP-4 staining in late-adenocarcinomas was stronger than that in normal mucosa and adenomas, while there was no difference in the staining of its receptors (BMPR-IA and BMPR-II) at all stages. The up-regulation of BMP-4 was further validated in another panel of tumor tissues by real-time RT-PCR, showing that BMP-4 mRNA levels in primary colonic carcinomas with liver metastasis were significantly higher than that in the matched normal mucosa. In order to understand the functional relevance of BMP-4 expression in colon cancer progression, BMP-4-overexpressing cell clones were generated from HCT116 cells. Overexpression of BMP-4 did not affect the HCT116 cell growth. The cells overexpressing BMP-4 became resistant to serum-starvation-induced apoptosis and exhibited enhanced migration and invasion characteristics. Overexpression of BMP-4 changed cell morphology to invasive spindle phenotype and induced the expression and activity of urokinase plasminogen activator (uPA). These results indicate that BMP-4 confers invasive phenotype during progression of colon cancer. 相似文献
105.
Muthuraman Pandurangan Hemalatha Moorthy Ravikumar Sambandam Vikramathithan Jeyaraman Ganesh Irisappan Ramkumar Kothandam 《Cytotechnology》2014,66(5):839-844
The present investigation was carried out to evaluate the effect of stress hormone cortisol on the myogenic markers in the C2C12 cells co-cultured with 3T3-L1 preadipocytes. Co-culturing was achieved by transwell inserts with a 0.4 μm porous membrane. C2C12 and 3T3-L1 cells were grown independently on the transwell plates. After differentiation, inserts containing 3T3-L1 cells were transferred to C2C12 plates for co-culturing. 10 μg/μl of cortisol was added to the medium. After 72 h of treatment, C2C12 cells which were in the lower well were harvested for analysis. RT-PCR analysis of myogenic markers such as of myogenin, MyoD, Myf5, PAX3 and PAX7 showed a significant reduction in the mRNA expression of these myogenic markers. In addition, cortisol increased calpain activity, which led to accelerated protein degradation, which in turn reduced the myogenic rate. In conclusion, cortisol treatment reduced mRNA expression of myogenic markers in the co-cultured C2C12 cells, which is quite distinct from one dimensional mono-cultured C2C12 cells. 相似文献
106.
107.
Kshitij Wagh Aatish Bhatia Gabriela Alexe Anupama Reddy Vijay Ravikumar Michael Seiler Michael Boemo Ming Yao Lee Cronk Asad Naqvi Shridar Ganesan Arnold J. Levine Gyan Bhanot 《PloS one》2012,7(9)
The Maasai are a pastoral people in Kenya and Tanzania, whose traditional diet of milk, blood and meat is rich in lactose, fat and cholesterol. In spite of this, they have low levels of blood cholesterol, and seldom suffer from gallstones or cardiac diseases. Field studies in the 1970s suggested that the Maasai have a genetic adaptation for cholesterol homeostasis. Analysis of HapMap 3 data using Fixation Index (Fst) and two metrics of haplotype diversity: the integrated Haplotype Score (iHS) and the Cross Population Extended Haplotype Homozygosity (XP-EHH), identified genomic regions and single nucleotide polymorphisms (SNPs) as strong candidates for recent selection for lactase persistence and cholesterol regulation in 143–156 founder individuals from the Maasai population in Kinyawa, Kenya (MKK). The non-synonmous SNP with the highest genome-wide Fst was the TC polymorphism at rs2241883 in Fatty Acid Binding Protein 1(FABP1), known to reduce low density lipoprotein and tri-glyceride levels in Europeans. The strongest signal identified by all three metrics was a 1.7 Mb region on Chr2q21. This region contains the genes LCT (Lactase) and MCM6 (Minichromosome Maintenance Complex Component) involved in lactase persistence, and the gene Rab3GAP1 (Rab3 GTPase-activating Protein Catalytic Subunit), which contains polymorphisms associated with total cholesterol levels in a genome-wide association study of >100,000 individuals of European ancestry. Sanger sequencing of DNA from six MKK samples showed that the GC-14010 polymorphism in the MCM6 gene, known to be associated with lactase persistence in Africans, is segregating in MKK at high frequency (∼58%). The Cytochrome P450 Family 3 Subfamily A (CYP3A) cluster of genes, involved in cholesterol metabolism, was identified by Fst and iHS as candidate loci under selection. Overall, our study identified several specific genomic regions under selection in the Maasai which contain polymorphisms in genes associated with lactase persistence and cholesterol regulation. 相似文献
108.
109.
It is demonstrated that a solution of dichloroacetic acid in toluene removes dimethoxytrityl groups from the 5'-terminus of an antisense phosphorothioate oligodeoxyribonucleotide (ISIS 5132/CGP69846A) during synthesis on solid support cleanly and efficiently. It is therefore suggested to replace health hazardous dichloromethane which is typically used in oligonucleotide synthesis as solvent for DMTr-removal by toluene. 相似文献
110.
Amali AA Lin CJ Chen YH Wang WL Gong HY Rekha RD Lu JK Chen TT Wu JL 《Journal of biomedical science》2008,15(5):595-604
Myostatin, a member of the TGF-β superfamily, is a potent negative regulator of skeletal muscle and growth. Previously, we
reported Mstn1 from zebrafish and studied its influence on muscle development. In this study, we identified another form of
Myostatin protein which is referred to as Mstn2. The size of Mstn2 cDNA is 1342 bp with 109 and 132 bp of 5′ and 3′-untranslated
regions (UTRs), respectively. The coding region is 1101 bp encoding 367 amino acids. The identity between zebrafish Mstn1
and 2 is 66%. The phylogenetic tree revealed that the Mstn2 is an ancestral form of Mstn1. To study the functional aspects,
we overexpressed mstn2 and noticed that embryos became less active and the juveniles with bent and curved phenotypes when compared to the control.
The RT-PCR and in situ hybridization showed concurrent reduction of dystrophin associated protein complex (DAPC). In cryosection
and in situ hybridization, we observed the disintegration of somites, lack of transverse myoseptum and loss of muscle integrity
due to the failure of muscle attachment in mstn2 overexpressed embryos. Immunohistochemistry and western blot showed that there was a reduction of dystrophin, dystroglycan
and sarcoglycan at translational level in overexpressed embryos. Taken together, these results indicate the suitability of
zebrafish as an excellent animal model and our data provide the first in vivo evidence of muscle attachment failure by the
overexpression of mstn2 and it leads to muscle loss which results in muscle dystrophy that may contribute to Duchenne syndrome and other muscle related
diseases.
A. Anusha Amali and Cliff Ji-Fan Lin contributed equally. 相似文献