11 research outputs found
Angiogenic factors in TAO.
<p>MMP-8 = matrix metalloproteinase-8, VEGF = vascular endothelial growth factor; NS = nonsmokers, S = smokers, TAO = Thromboangiitis obliterans.</p
Serum of TAO patients inhibits HUVEC migration.
<p>Scratch wound closure assay; a single scrape was made across a confluent HUVEC monolayer (Baseline). The extent of regrowth to close the scratch wound was measured after 6 hours (6 h) incubation in medium containing 10% of serum of TAO patients or controls. Data are presented as medians, with 25/75 percentiles (boxes) and 10/90 percentiles (bars), (n = 12 in each group). ***P<0.001; NS = nonsmokers, S = smokers, TAO = Thromboangiitis obliterans.</p
Serum of TAO patients inhibits HUVEC proliferation by changes in cell cycle progression.
<p>A) HUVECs were incubated for 24 hours with 10% serum of TAO patients and controls and proliferation was determined as doubling time in hours. Data are presented as medians, with 25/75 percentiles (boxes) and 10/90 percentiles (bars), (n = 12 in each group). *P<0.05, **P<0.01, ***P<0.001. B) For cell cycle analysis HUVECs were cultured for 24 hours with 10% serum of TAO patients and controls, and DNA content was measured by flow cytometry. NS = nonsmokers, S = smokers, TAO = Thromboangiitis obliterans.</p
Proliferation, viability and cell cycle analysis.
*<p>TAO vs. NS,</p>†<p>TAO vs. S; FC = fetal calf, NS = nonsmokers, S = smokers, TAO = Thromboangiitis obliterans.</p
Levels of circulating progenitor cells and PBMCs in TAO patients.
<p>Levels of CD45<sup>dim</sup>CD34<sup>+</sup>, CD45<sup>dim</sup>CD34<sup>+</sup>CD133<sup>+</sup>, and CD45<sup>dim</sup>CD34<sup>+</sup>VEGFR2<sup>+</sup> progenitor cells were measured by flow cytometry. The numbers of progenitor cells (PC) were expressed as cells per 10<sup>5</sup> peripheral blood mononuclear cells (PBMCs). A) Levels of CD45<sup>dim</sup>CD34<sup>+</sup> PC, B) levels of CD45<sup>dim</sup>CD34<sup>+</sup>CD133<sup>+</sup> PC, C) levels CD45<sup>dim</sup>CD34<sup>+</sup>VEGFR2<sup>+</sup> PC, D) proportion of CD45<sup>dim</sup>CD34<sup>+</sup>VEGFR2<sup>+</sup> PC on CD45<sup>dim</sup>CD34<sup>+</sup> PC, E) number of PBMCs per ml of blood. Data are presented as medians, with 25/75 percentiles (boxes) and 10/90 percentiles (bars), (n = 12 in each group). *P<0.05, **P<0.01, ***P<0.001; NS = nonsmokers, S = smokers, TAO = Thromboangiitis obliterans.</p
Low Dose Proteasome Inhibition Affects Alternative Splicing
Protein degradation by the ubiquitin proteasome system
ensures controlled degradation of structural proteins, signaling mediators,
and transcription factors. Inhibition of proteasome function by specific
proteasome inhibitors results in dose-dependent cellular effects ranging
from induction of apoptosis to protective stress responses. The present
study seeks to identify nuclear regulators mediating the protective
stress response to low dose proteasome inhibition. Primary human endothelial
cells were treated with low doses of the proteasome inhibitor MG132
for 2 h, and proteomic analysis of nuclear extracts was performed.
Using a 2-D differential in gel electrophoresis (DIGE) approach, we
identified more than 24 splice factors to be differentially regulated
by low dose proteasome inhibition. In particular, several isoforms
of hnRNPA1 were shown to be increased, pointing toward altered posttranslational
modification of hnRNPA1 upon proteasome inhibition. Elevated levels
of splice factors were associated with a different alternative splicing
pattern in response to proteasome inhibition as determined by Affymetrix
exon array profiling. Of note, we observed alternative RNA processing
for stress associated genes such as caspases and heat shock proteins.
Our study provides first evidence that low dose proteasome inhibition
affects posttranscriptional regulation of splice factors and early
alternative splicing events
Low Dose Proteasome Inhibition Affects Alternative Splicing
Protein degradation by the ubiquitin proteasome system
ensures controlled degradation of structural proteins, signaling mediators,
and transcription factors. Inhibition of proteasome function by specific
proteasome inhibitors results in dose-dependent cellular effects ranging
from induction of apoptosis to protective stress responses. The present
study seeks to identify nuclear regulators mediating the protective
stress response to low dose proteasome inhibition. Primary human endothelial
cells were treated with low doses of the proteasome inhibitor MG132
for 2 h, and proteomic analysis of nuclear extracts was performed.
Using a 2-D differential in gel electrophoresis (DIGE) approach, we
identified more than 24 splice factors to be differentially regulated
by low dose proteasome inhibition. In particular, several isoforms
of hnRNPA1 were shown to be increased, pointing toward altered posttranslational
modification of hnRNPA1 upon proteasome inhibition. Elevated levels
of splice factors were associated with a different alternative splicing
pattern in response to proteasome inhibition as determined by Affymetrix
exon array profiling. Of note, we observed alternative RNA processing
for stress associated genes such as caspases and heat shock proteins.
Our study provides first evidence that low dose proteasome inhibition
affects posttranscriptional regulation of splice factors and early
alternative splicing events
Blood lipid levels after intervention.
<p>Box plot of total cholesterol (<b>A</b>) and LDL cholesterol (<b>B</b>) levels in serum after supplementation with the indicated diets for 4 weeks. The boxes contain 50% of individual values; the middle line within the box represents the median. Total and LDL cholesterol levels were significantly lower in the lycopene group. *P<0.05 compared to cholesterol and placebo. n = 9 animals per group.</p
Plasma total lycopene levels in individual rabbits after feeding the indicated diets for 4 weeks.
<p>Cholesterol: animals were fed with a high-cholesterol diet (0.5% cholesterol); Placebo: high-cholesterol diet supplemented with placebo beadlets containing all ingredients of lycopene beadlets except lycopene; Lycopene: high-cholesterol diet supplemented with 5 mg lycopene/kg body weight/day as lycopene beadlets. The number in the graph represents the mean ± SD. n = 9 animals per group.</p
Serum lipid levels and LDL/HDL quotients.
<p>Values (in mg/dl) are mean ± SD from n = 9 animals per group.</p><p>*P<0.05 compared to cholesterol and placebo.</p>#<p>P<0.05 compared to placebo.</p