Changes in gene expression induced by H(2)O(2) in cardiac myocytes.
Oxidative stress induces cardiac myocyte apoptosis. At least some effects are probably mediated through changes in gene expression. Using Affymetrix arrays, we examined the changes in gene expression induced by H(2)O(2) (0.04, 0.1, and 0.2mM; 2 and 4h) in rat neonatal ventricular myocytes. Changes in selected upregulated genes were confirmed by ratiometric RT-PCR. p21(Cip1/Waf1) was one of the only two genes upregulated in all conditions studied. Of the heat shock proteins, only Hsp70/70.1 was induced by H(2)O(2) with no change in the expression of Hsp25, Hsp60 or Hsp90. Heme oxygenase 1 was also potently upregulated, but not heme oxygenases 2 or 3. Of the intercellular adhesion proteins, syndecan-1 was significantly upregulated in response to H(2)O(2), with little change in the expression of other syndecans and no change in expression of any of the integrins studied. Thus, oxidative stress, exemplified by H(2)O(2), selectively promotes the expression of specific gene family members.
Kemp
Timothy J
TJ
NHLI Division (Cardiac Medicine), Faculty of Medicine, Imperial College London, London, UK.
Causton
Helen C
HC
Clerk
Angela
A
D000818:Animals; D000831:Animals, Newborn; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053668:Syndecan-1; D053667:Syndecans
C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018840:HSP70 Heat-Shock Proteins; D008562:Membrane Glycoproteins; D016877:Oxidants; D011509:Proteoglycans; C508243:Sdc1 protein, rat; D053668:Syndecan-1; D053667:Syndecans; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1