RGD Reference Report - Differential regulation of Kruppel-like factor family transcription factor expression in neonatal rat cardiac myocytes: effects of endothelin-1, oxidative stress and cytokines. - Rat Genome Database

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Differential regulation of Kruppel-like factor family transcription factor expression in neonatal rat cardiac myocytes: effects of endothelin-1, oxidative stress and cytokines.

Authors: Cullingford, TE  Butler, MJ  Marshall, AK  Tham el, L  Sugden, PH  Clerk, A 
Citation: Cullingford TE, etal., Biochim Biophys Acta. 2008 Jun;1783(6):1229-36. Epub 2008 Mar 25.
RGD ID: 2316543
Pubmed: PMID:18406357   (View Abstract at PubMed)
PMCID: PMC2396231   (View Article at PubMed Central)
DOI: DOI:10.1016/j.bbamcr.2008.03.007   (Journal Full-text)

Kruppel-like transcription factors (Klfs) modulate fundamental cell processes. Cardiac myocytes are terminally-differentiated, but hypertrophy in response to stimuli such as endothelin-1. H2O2 or cytokines promote myocyte apoptosis. Microarray studies of neonatal rat myocytes identified several Klfs as endothelin-1-responsive genes. We used quantitative PCR for further analysis of Klf expression in neonatal rat myocytes. In response to endothelin-1, Klf2 mRNA expression was rapidly increased ( approximately 9-fold; 15-30 min) with later increases in expression of Klf4 and Klf6 ( approximately 5-fold; 30-60 min). All were regulated as immediate early genes (cycloheximide did not inhibit the increases in expression). Klf5 expression was increased at 1-2 h ( approximately 13-fold) as a second phase response (cycloheximide inhibited the increase). These increases were transient and attenuated by U0126. H2O2 increased expression of Klf2, Klf4 and Klf6, but interleukin-1beta or tumor necrosis factor alpha downregulated Klf2 expression with no effect on Klf4 or Klf6. Of the Klfs which repress transcription, endothelin-1 rapidly downregulated expression of Klf3, Klf11 and Klf15. The dynamic regulation of expression of multiple Klf family members in cardiac myocytes suggests that, as a family, they are actively involved in regulating phenotypic responses (hypertrophy and apoptosis) to extracellular stimuli.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Klf2Ratcellular response to cycloheximide  IEP  RGD 
Klf4Ratcellular response to cycloheximide  IEP  RGD 
Klf6Ratcellular response to cycloheximide  IEP  RGD 
Klf2Ratcellular response to hydrogen peroxide  IEP  RGD 
Klf4Ratcellular response to hydrogen peroxide  IEP  RGD 
Klf6Ratcellular response to hydrogen peroxide  IEP  RGD 
Klf2Ratcellular response to interleukin-1  IEP  RGD 
Klf2Ratcellular response to organic cyclic compound  IEP U0126 and LY294002RGD 
Klf4Ratcellular response to organic cyclic compound  IEP U0126 and LY294002RGD 
Klf5Ratcellular response to organic cyclic compound  IEP U0126 RGD 
Klf6Ratcellular response to organic cyclic compound  IEP U0126RGD 
Il1rl1Ratcellular response to peptide  IEP endothelin-1RGD 
Irs2Ratcellular response to peptide  IEP endothelin-1RGD 
Klf1Ratcellular response to peptide  IEP endothelin-1RGD 
Klf10Ratcellular response to peptide  IEP endothelin-1RGD 
Klf11Ratcellular response to peptide  IEP endothelin-1RGD 
Klf15Ratcellular response to peptide  IEP endothelin-1RGD 
Klf2Ratcellular response to peptide  IEP endothelin-1RGD 
Klf3Ratcellular response to peptide  IEP endothelin-1RGD 
Klf4Ratcellular response to peptide  IEP endothelin-1RGD 
Klf5Ratcellular response to peptide  IEP endothelin-1RGD 
Klf6Ratcellular response to peptide  IEP endothelin-1RGD 
Klf9Ratcellular response to peptide  IEP endothelin-1RGD 
Klf2Ratcellular response to tumor necrosis factor  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1rl1  (interleukin 1 receptor-like 1)
Irs2  (insulin receptor substrate 2)
Klf1  (KLF transcription factor 1)
Klf10  (KLF transcription factor 10)
Klf11  (KLF transcription factor 11)
Klf15  (KLF transcription factor 15)
Klf2  (KLF transcription factor 2)
Klf3  (KLF transcription factor 3)
Klf4  (KLF transcription factor 4)
Klf5  (KLF transcription factor 5)
Klf6  (KLF transcription factor 6)
Klf9  (KLF transcription factor 9)


Additional Information