Objcctive:To determine the gene expression patterns of endothelin (ET)system components in cultured astrocytes(AC),and to examine the direct effcct of hypoxia on ET system gene expression in cultured ***:The ET system...
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Objcctive:To determine the gene expression patterns of endothelin (ET)system components in cultured astrocytes(AC),and to examine the direct effcct of hypoxia on ET system gene expression in cultured ***:The ET system was considered to be related to the activation of AC. However,how hypoxia affects the ET system in transcriptional levels remains ***:AC was prepared form mouse brain,and cultured 4 *** further incubated under normoxic or hypoxic conditions for 24h. ET peptide levels were determined by *** transcripts of ET system components were measured by Northern Blot RNA hybridization and ***:In normoxic AC,ET-1,ET converting enzyme(ECE)-2,ETA receptor,and ETB receptor mRNAs were detected by Northern blot hybridization with ETB receptor mRNA appearing to be the predominant receptor ***-3and ECE-1 were only detected by RT-PCR,indicating low expression levels of these *** induced a 1.7-fold increase in ET peptide level in culture supernatants as comparcd to controls(p<0.001).At the same time,a 3-fold increase of ET-1 mRNA(p<0.001)was determined by Northern blot RNA analysis,indicating a regulation at the transcriptional *** ETA and ETB receptor mRNASweredownregulated to approximately 20% of control levels(p<0.001), while ECE-2 mRNA remained ***:These results indicate direct effects of hypoxia on astrocytic ET system gene ***,similar changes observed in ischemic conditions in vivo are likely to be at least partially independent from the modified cerebral microenvironment.
Pressure overload(PO) first causes cardiac hypertrophy and then heart failure(HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex...
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Pressure overload(PO) first causes cardiac hypertrophy and then heart failure(HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex differences. We used a transverse aortic constriction(TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks, but with sex differences in hypertrophy 6 and 9 weeks after TAC. Cardiac gene expression was analyzed 2 weeks after surgery. Deregulated genes were classified into functional gene ontology(GO) categories and used for pathway analysis. Classical marker genes of hypertrophy were similarly upregulated in both sexes(α-actin, ANP, BNP, CTGF). Thirty-five genes controlling mitochondrial function(PGC-1, cytochrome oxidase, carnitine palmitoyl transferase, acyl-CoA dehydrogenase, pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC. genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males(collagen 3, matrix metalloproteinase 2, TIMP2, and TGFβ2, all about twofold) after TAC. We confirmed 87% of the gene expression by real-time polymerase chain reaction. By GO classification, female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis. Promoter studies confirmed the upregulation of PGC-1 by E2. Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO. These differences could contribute to subsequent sex differences in cardiac function and HF.
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