Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

被引：37

作者：

Cullingford, Timothy E. ^{[1
]}

Markou, Thomais ^{[1
]}

Fuller, Stephen J. ^{[1
]}

Giraldo, Alejandro ^{[1
]}

Pikkarainen, Sampsa ^{[1
]}

Zoumpoulidou, Georgia ^{[1
]}

Alsafi, Ali ^{[1
]}

Ekere, Collins ^{[1
]}

Kemp, Timothy J. ^{[1
]}

Dennis, Jayne L. ^{[2
]}

Game, Laurence ^{[2
]}

Sugden, Peter H. ^{[1
]}

Clerk, Angela ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst Div, London SW7 2AZ, England

[2] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Ctr Clin Sci,Imperial Coll Microarray Ctr, London W12 0NN, England

来源：

GENOME BIOLOGY | 2008年 / 9卷 / 02期

关键词：

D O I：

10.1186/gb-2008-9-2-r32

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Background: Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results: Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited > 50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion: The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in this response.

引用

页数：14

共 49 条

[41] CARDIAC MYOCYTE HYPERTROPHY IS ASSOCIATED WITH C-MYC PROTOONCOGENE EXPRESSION [J].