Kemp Timothy J, Causton Helen C, Clerk Angela
NHLI Division (Cardiac Medicine), Faculty of Medicine, Imperial College London, London, UK.
Biochem Biophys Res Commun. 2003 Jul 25;307(2):416-21. doi: 10.1016/s0006-291x(03)01215-4.
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.
氧化应激诱导心肌细胞凋亡。至少部分效应可能是通过基因表达的变化介导的。我们使用Affymetrix基因芯片,检测了过氧化氢(0.04、0.1和0.2 mM;2小时和4小时)诱导的大鼠新生心室肌细胞基因表达的变化。通过定量逆转录聚合酶链反应(ratiometric RT-PCR)证实了所选上调基因的变化。p21(Cip1/Waf1)是在所有研究条件下仅有的两个上调基因之一。在热休克蛋白中,只有Hsp70/70.1被过氧化氢诱导,而Hsp25、Hsp60或Hsp90的表达没有变化。血红素加氧酶1也被显著上调,但血红素加氧酶2或3没有上调。在细胞间粘附蛋白中,syndecan-1对过氧化氢有显著上调反应,其他syndecan的表达变化很小,所研究的任何整合素的表达都没有变化。因此,以过氧化氢为例的氧化应激选择性地促进特定基因家族成员的表达。