78 Citations (Scopus)

Abstract

In the present study, baicalein (BE) but not its glycoside, baicalin (BI), induced heme oxygenase-1 (HO-1) gene expression at both the mRNA and protein levels, and the BE-induced HO-1 protein was blocked by adding cycloheximide (CHX) or actinomycin D (Act D). Activation of ERK, but not JNK or p38, proteins via induction of phosphorylation in accordance with increasing intracellular peroxide levels was detected in BE-treated RAW264.7 macrophages. The addition of the ERK inhibitor, PD98059, (but not the p38 inhibitor, SB203580, or the JNK inhibitor, SP600125) and the chemical antioxidant, N-acetyl cysteine (NAC), significantly reduced BE-induced HO-1 protein expression by respectively blocking ERK protein phosphorylation and intracellular peroxide production. Additionally, BE but not BI effectively protected RAW264.7 cells from hydrogen peroxide (H2O2)-induced cytotoxicity, and the preventive effect was attenuated by the addition of the HO inhibitor, SnPP, and the ERK inhibitor, PD98059. H2O2-induced apoptotic events including hypodiploid cells, DNA fragmentation, activation of caspase 3 enzyme activity, and a loss in the mitochondrial membrane potential with the concomitant release of cytochrome c from mitochondria to the cytosol were suppressed by the addition of BE but not BI. Blocking HO-1 protein expression by the HO-1 antisense oligonucleotide attenuated the protective effect of BE against H2O2-induced apoptosis by suppressing HO-1 gene expression in macrophages. Overexpression of the HO-1 protein inhibited H2O2-induced apoptotic events such as DNA fragmentation and hypodiploid cells by reducing intracellular peroxide production induced by H2O2, compared with those events in neo-control (neo-RAW264.7) cells. In addition, CO, but not bilirubin and biliverdin, addition inhibits H2O2-induced cytotoxicity in macrophages. It suggests that CO can be responsible for the protective effect associated with HO-1 overexpression. The notion of induction of HO-1 gene expression through a ROS-dependent manner suppressing H2O2-induced cell death is identified in the present study.

Original languageEnglish
Pages (from-to)1073-1086
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1773
Issue number7
DOIs
Publication statusPublished - Jul 2007

    Fingerprint

Keywords

  • Apoptosis
  • CO
  • ERKs
  • Flavonoids
  • Heme oxygenase 1
  • ROS

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

Cite this