Ferulic acid induces heme oxygenase-1 via activation of ERK and Nrf2.
ABSTRACT This study investigated the effect of ferulic acid (FA) on the up-regulation of heme oxygenase-1 (HO-1) in lymphocytes and the molecular mechanisms involved. Lymphocytes were treated with FA (0.001-0.1 μM) for certain times. Cell viability, the activity and level of expression of HO-1, and signal pathways were analyzed. FA significantly upregulated HO-1 expression both at the level of mRNA and protein in lymphocytes. Moreover, FA induced NF-E2-related factor (Nrf2) nuclear translocation and transcriptional activity, which is upstream of FA induced HO-1 expression. In addition, lymphocytes treated with FA exhibited activation of extracellular regulated kinase (ERK) and treatments with U0126 (an ERK kinase inhibitor) attenuated the FA induced activation of Nrf2, resulting in a decrease in HO-1 expression. Zinc protoporphyrin (ZnPP, a HO-1 inhibitor) markedly suppressed cytoprotection from radiation-induced cell damage by FA. Results suggested that the ERK signaling pathway controlled the anti-oxidation of FA by regulating the expression of the antioxidant enzyme HO-1.
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ABSTRACT: Ferulic acid provides neuroprotective effects against a middle cerebral artery occlusion (MCAO)-induced cerebral ischemia. Mitogen-activated protein kinases can regulate extensive intracellular processes including cell differentiation, growth, and death. This study further investigated whether ferulic acid modulates a protective mechanism through the activation of Raf-MEK-ERK and its downstream targets, including 90 ribosomal S6 kinase (p90RSK) and Bad during cerebral ischemic injury. Male Sprague-Dawley rats were treated with ferulic acid (100mg/kg) or vehicle after the onset of MCAO and brain tissues were collected 24h after MCAO. These results indicated that ferulic acid decreases the volume of the infarct area and the number of cells positive in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Although MCAO injury induces a decrease in the phosphorylation of Raf-1, MEK1/2, and ERK1/2, ferulic acid treatment prevents the injury-induced decrease in these phosphorylation levels. Ferulic acid also attenuates the injury-induced decrease in p90RSK and Bad phosphorylation levels. These findings suggest that ferulic acid prevents MCAO-induced neuronal cell death and that the MEK-ERK-p90RSK-Bad signaling pathway is involved in these neuroprotective effects. Copyright © 2014. Published by Elsevier Ireland Ltd.Neuroscience Letters 12/2014; 588. DOI:10.1016/j.neulet.2014.12.047 · 2.06 Impact Factor
- Food science and biotechnology 08/2014; 23(4):1327-1333. DOI:10.1007/s10068-014-0182-5 · 0.66 Impact Factor
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ABSTRACT: The cytoprotective mechanism of 7, 8-dihydroxyflavone (DHF) against oxidative stress-induced cell damage with respect to its stimulatory effect on the expression of heme oxygenase-1 (HO-1), a potent antioxidant enzyme, was investigated in the present study. Up-regulation of HO-1 expression by DHF was both dose and time dependent in lung fibroblast V79-4 cells. DHF also increased the protein expression level of the transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), and induced the translocation of Nrf2 from the cytosol into the nucleus, leading to elevated HO-1 expression. The siNrf2 RNA-transfection attenuated HO-1 expression induced by DHF treatment. In addition, DHF induced the activation of extracellular signal-regulated kinase (ERK), while U0126 (a specific pharmacological inhibitor of ERK kinase) abrogated DHF-activated Nrf2 and HO-1 expression. This suggests that DHF increased the levels of Nrf2 and HO-1 via ERK-dependent pathways. Furthermore, DHF significantly prevented the reduction of cell viability in response to oxidative stress; however, U0126 attenuated the protective effect of DHF. Taken together, these results demonstrate that DHF protected cells from oxidative stress via the activation of an ERK/Nrf2/HO-1 signaling pathway.In Vitro Cellular & Developmental Biology - Animal 03/2014; 50(6). DOI:10.1007/s11626-014-9735-4 · 1.00 Impact Factor