Piceatannol markedly upregulates heme oxygenase-1 expression and alleviates oxidative stress in skeletal muscle cells.
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ABSTRACT:
SUBMITTER: Nonaka S
PROVIDER: S-EPMC6500920 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prolonged mechanical ventilation (MV) results in a rapid onset of diaphragmatic atrophy that is primarily due to increased proteolysis. Although MV-induced protease activation can involve several factors, it is clear that oxidative stress is a required signal for protease activation in the diaphragm during prolonged MV. However, the oxidant-producing pathways in the diaphragm that contribute to MV-induced oxidative stress remain unknown. We have demonstrated that prolonged MV results in increased diaphragmatic expression of a key stress-sensitive enzyme, heme oxygenase (HO)-1. Paradoxically, HO-1 can function as either a pro-oxidant or an antioxidant, and the role that HO-1 plays in MV-induced diaphragmatic oxidative stress is unknown. We tested the hypothesis that HO-1 acts as a pro-oxidant in the diaphragm during prolonged MV.To determine whether HO-1 functions as a pro-oxidant or an antioxidant in the diaphragm during MV, we assigned rats into three experimental groups: (1) a control group, (2) a group that received 18 h of MV and saline solution, and (3) a group that received 18 h of MV and was treated with a selective HO-1 inhibitor. Indices of oxidative stress, protease activation, and fiber atrophy were measured in the diaphragm.Inhibition of HO-1 activity did not prevent or exacerbate MV-induced diaphragmatic oxidative stress (as indicated by biomarkers of oxidative damage). Further, inhibition of HO-1 activity did not influence MV-induced protease activation or myofiber atrophy in the diaphragm.Our results indicate that HO-1 is neither a pro-oxidant nor an antioxidant in the diaphragm during MV. Furthermore, our findings reveal that HO-1 does not play an important role in MV-induced protease activation and diaphragmatic atrophy.
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Project description:Periodontal disease is associated with chronic oxidative stress and inflammation. Caffeic acid phenethyl ester (CAPE), which is a potent inducer of heme oxygenase 1 (HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients. Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin (SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages. CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE. In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.
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