title: Dimethyl sulfoxide induces heme oxygenase-1 expression via JNKs and Nrf2 pathways in human umbilical vein endothelial cells.
abstract: Dimethyl sulfoxide (DMSO) has recently been proposed as an anti-inflammatory and free radical scavenging agent. However, the mechanisms by which DMSO mediates its therapeutic effects are unclear. In this paper, we investigated the capability of DMSO to up-regulate heme oxygenase-1(HO-1) expression, as well as the possible underlying mechanisms in human umbilical vein endothelial cells (HUVECs). DMSO induced HO-1 expression both at the level of mRNA and protein in dose-and time-dependent manners in HUVECs, resulting in increased HO-1 activity. The pharmacological inhibition of cJun-N-terminal kinases (JNKs) blocked the DMSO-induced HO-1 up-regulation, while inhibition of extracellular regulated kinase and p38-MAPK did not block heme oxygenase-1 up-regulation. In addition, the phosphorylation of JNKs was initiated by DMSO, indicating the involvement of this kinase in the observed response. DMSO increased the nuclear translocation of NF-E2-related factor 2 (Nrf2) and enhanced its binding to the anti-oxidant response element. Inhibition of Nrf2 synthesis by small interfering RNA molecules subsequently inhibited HO-1 expression induced by DMSO, indicating DMSO's role in inducing HO-1 expression via Nrf2 activation. Utilizing these findings, the present study identified DMSO as a novel inducer of HO-1 expression and identified the underlying mechanisms involved in this process.
authors.affiliation: Department of Anesthesiology, Shanghai Minhang District Central Hospital, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.forename: Zhanggang
authors.initials: Z
authors.lastname: Xue
authors.forename: Jing
authors.initials: J
authors.lastname: Cang
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D057075:Enzyme Assays; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D051547:Heme Oxygenase-1; D048670:MAP Kinase Kinase 4; D004121:Dimethyl Sulfoxide