Home About us Contact
|
Home About us Contact | ||
|
|
||
Altered Ratio (altered + ratio)
Selected AbstractsVanadium-induced apoptosis of HaCaT cells is mediated by c-fos and involves nuclear accumulation of clusterinFEBS JOURNAL, Issue 14 2009Soultana Markopoulou Vanadium exerts a variety of biological effects, including antiproliferative responses through activation of the respective signaling pathways and the generation of reactive oxygen species. As epidermal cells are exposed to environmental insults, human keratinocytes (HaCaT) were used to investigate the mechanism of the antiproliferative effects of vanadyl(IV) sulfate (VOSO4). Treatment of HaCaT cells with VOSO4 inhibited proliferation and induced apoptosis in a dose-dependent manner. Inhibition of proliferation was associated with downregulation of cyclins D1 and E, E2F1, and the cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p27Kip1. Induction of apoptosis correlated with upregulation of the c-fos oncoprotein, changes in the expression of clusterin (CLU), an altered ratio of antiapoptotic to proapoptotic Bcl-2 protein family members, and poly(ADP-ribose) polymerase-1 cleavage. Forced overexpression of c-fos induced apoptosis in HaCaT cells that correlated with secretory CLU downregulation and upregulation of nuclear CLU (nCLU), a pro-death protein. Overexpression of Bcl-2 protected HaCaT cells from vanadium-induced apoptosis, whereas secretory CLU overexpression offered no cytoprotection. In contrast, nCLU sensitized HaCaT cells to apoptosis. Our data suggest that vanadium-mediated apoptosis was promoted by c-fos, leading to alterations in CLU isoform processing and induction of the pro-death nCLU protein. [source] Role of surface promoter mutations in hepatitis B surface antigen production and secretion in occult hepatitis B virus infection,JOURNAL OF MEDICAL VIROLOGY, Issue 3 2007Sonali Sengupta Abstract The production, secretion, and localization of surface proteins of hepatitis B virus (HBV) and the ratio of large to small surface protein S was studied in HepG2 cells transfected with the wild-type and mutant pre-S1 and pre-S2/S promoters of HBV molecular clones 313.1 (GenBank accession no. AY161147) and 761.1 (GenBank accession no. AY161159) from two patients with occult HBV infection. Fusion constructs were made by in frame fusion of the wild-type surface gene to the mutant pre-S1 and pre-S2/S promoters and wild-type promoter so that the structural part of the small surface protein remains identical. HepG2 cells transfected transiently were used for analysis. HBV surface proteins production and secretion was determined by enzyme linked immuno assay (ELISA) and localization by immunofluorescence. Immunoprecipitation of the large, middle, and small surface protein was carried out in transient transfected and metabolically labeled cells to determine the ratio of the large to small surface protein. The results indicate that HepG2 cells transfected with mutant HBV promoters had reduced HBV surface proteins secretion compared to wild-type HBV. HepG2 cells transfected with mutant HBV pre-S1 and pre-S2/S promoters showed cytoplasmic aggregation of HBV surface proteins compared to wild-type HBV promoters, which showed diffuse cytoplasmic localization. In all cases, the HBV surface proteins localized to the endoplasmic reticulum. The ratio between the large and small surface protein was 1.89 and 0.56 with mutant HBV 313.1 and 761.1 pre-S1 and pre-S2/S promoters, respectively, compared to 0.17 in wild-type. Thus, the aggregation of surface proteins, altered ratio and secretion of surface proteins were possibly the causes of occult hepatitis B infection. J. Med. Virol. 79:220,228, 2007. © 2007 Wiley-Liss, Inc. [source] Nutritional Deprivation of ,-Linolenic Acid Decreases but Does Not Abolish Turnover and Availability of Unacylated Docosahexaenoic Acid and Docosahexaenoyl-CoA in Rat BrainJOURNAL OF NEUROCHEMISTRY, Issue 6 2000Miguel A. Contreras Abstract: We applied our in vivo fatty acid method to examine concentrations, incorporation, and turnover rates of docosahexaenoic acid (22:6 n-3) in brains of rats subject to a dietary deficiency of ,-linolenic acid (18:3 n-3) for three generations. Adult deficient and adequate rats of the F3 generation were infused intravenously with [4,5- 3H]docosahexaenoic acid over 5 min, after which brain uptake and distribution of tracer were measured. Before infusion, the plasma 22:6 n-3 level was 0.2 nmol ml -1 in 18:3 n-3-deficient compared with 10.6 nmol ml -1 in control rats. Brain unesterified 22:6 n-3 was not detectable, whereas docosahexaenoyl-CoA content was reduced by 95%, and 22:6 n-3 content in different phospholipid classes was reduced by 83-88% in deficient rats. Neither plasma or brain arachidonic acid (20:4 n-6) level was significantly changed with diet. Docosapentaenoic acid (22:5 n-6) reciprocally replaced 22:6 n-3 in brain phospholipids. Calculations using operational equations from our model indicated that 22:6 n-3 incorporation from plasma into brain was reduced 40-fold by 18:3 n-3 deficiency. Recycling of 22:6 n-3 due to deacylation-reacylation within phospholipids was reduced by 30-70% with the deficient diet, but animals nevertheless continued to produce 22:6 n-3 and docosahexaenoyl-CoA for brain function. We propose that functional brain effects of n-3 deficiency reflect altered ratios of n-6 to n-3 fatty acids. [source] Decrease in glomerulonephritis and Th1-associated autoantibody production after progesterone treatment in NZB/NZW miceARTHRITIS & RHEUMATISM, Issue 6 2009Grant C. Hughes Objective While estrogen treatment exacerbates disease in models of systemic lupus erythematosus (SLE), the effects of progesterone are unclear. This study was undertaken to assess the effects of continuous progesterone treatment on autoantibody production and spontaneous glomerulonephritis (GN) in a mouse model of SLE. Methods Female (NZB × NZW)F1 (NZB/NZW) mice were treated with vehicle, 2 mg of depot medroxyprogesterone acetate (DMPA), or 10 mg of DMPA every 6 weeks. Survival, proteinuria, and serum anti,double-stranded DNA (anti-dsDNA) levels were monitored. At 39 weeks of age, kidneys were analyzed for abnormalities and glomerular accumulation of IgG subclasses and C3. Spleen leukocyte subsets were also analyzed. Results DMPA treatment reduced mortality in a dose-dependent manner in association with reduced proteinuria and glomerular damage. High-dose DMPA treatment resulted in a reduction of total serum IgG and IgG2a anti-dsDNA antibody levels, whereas IgG1 anti-dsDNA antibody levels were modestly increased. High-dose DMPA reduced glomerular accumulation of IgG1, IgG2a, IgG3, and complement, while low-dose DMPA decreased glomerular IgG2a and IgG3 levels compared with vehicle treatment. Conclusion Our findings indicate that treatment of premorbid female NZB/NZW mice with DMPA reduces mortality and attenuates spontaneous GN, likely through multiple mechanisms, including altered ratios of protective Th2-related IgG antibodies versus nephritogenic Th1-related IgG autoantibodies. Thus, estrogen and progesterone may have disparate effects on lupus autoimmunity, lending new significance to observed hormonal imbalances in patients with SLE. These data also suggest that treatment of SLE patients with DMPA may have therapeutic benefit. [source] | ||||||||||