Linked Life Data

20190405

Source:http://linkedlifedata.com/resource/pubmed/id/20190405

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-1
pubmed:abstractText
A tetramethylpyrazine analogue, CXC195, was synthesized by the Boekelheide reaction, in which the second methyl group of tetramethylpyrazine (TMP) was replaced with (4,4'-fluorine) diphenyl-methyl-1-piperazidine, the active group of flunarizine. We have observed protective effects of CXC195 on vascular endothelial cell survival under oxidative stress in previous study. The aim of the present study was to investigate the effects of CXC195 against apoptosis induced by hydrogen peroxide in human umbilical vein endothelial cells (HUVECs). Accordingly, a biochemical approach to elucidate the apoptotic signal pathways was attempted. HUVECs were exposed to 150 muM H(2)O(2) for 12 h, resulting in an increase of apoptotic cells assessed by the nuclear staining assay and flow cytometry. Mitochondrial membrane potential was detected by retention of rhodamine123. The concentration of free intracellular calcium was determined by fura-2/AM fluorometry. Co-incubation with CXC195 reduced the percentage of apoptotic cells and inhibited the loss of mitochondrial membrane potential and intracellular calcium overload induced by H(2)O(2). Induction of p53, the activation of caspase-3 by H(2)O(2) which accompanying downregulation of bcl-2, was blocked by CXC195. In addition, CXC195 clearly improved phosphorylation levels of the antiapoptotic extracellular signal-regulated kinase-1/2 (ERK1/2) in cells undergoing oxidative damage. Moreover, CXC195 showed stronger effects on inhibition of apoptotic cells and loss of mitochondrial membrane potential and activation of phosphorylated ERK1/2 than TMP. These results suggest that CXC195 prevents reactive oxygen species-induced apoptosis through inhibition of the mitochondria-dependent caspase-3 pathway and ERK pathway to show a better beneficial effect in protecting endothelial cells than TMP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1347-5215
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
432-8
pubmed:meshHeading
pubmed-meshheading:20190405-Antioxidants, pubmed-meshheading:20190405-Apoptosis, pubmed-meshheading:20190405-Calcium, pubmed-meshheading:20190405-Caspase 3, pubmed-meshheading:20190405-Cell Line, pubmed-meshheading:20190405-Down-Regulation, pubmed-meshheading:20190405-Drugs, Chinese Herbal, pubmed-meshheading:20190405-Endothelial Cells, pubmed-meshheading:20190405-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:20190405-Flow Cytometry, pubmed-meshheading:20190405-Humans, pubmed-meshheading:20190405-Hydrogen Peroxide, pubmed-meshheading:20190405-Ligusticum, pubmed-meshheading:20190405-Membrane Potential, Mitochondrial, pubmed-meshheading:20190405-Oxidative Stress, pubmed-meshheading:20190405-Phosphorylation, pubmed-meshheading:20190405-Phytotherapy, pubmed-meshheading:20190405-Piperazines, pubmed-meshheading:20190405-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:20190405-Pyrazines, pubmed-meshheading:20190405-Tumor Suppressor Protein p53, pubmed-meshheading:20190405-Umbilical Veins
pubmed:year
2010
pubmed:articleTitle
Mechanism of tetramethylpyrazine analogue CXC195 inhibition of hydrogen peroxide-induced apoptosis in human endothelial cells.
pubmed:affiliation
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't