title: Reduced aldehyde dehydrogenase expression in preeclamptic decidual mesenchymal stem/stromal cells is restored by aldehyde dehydrogenase agonists.
abstract: High resistance to oxidative stress is a common feature of mesenchymal stem/stromal cells (MSC) and is associated with higher cell survival and ability to respond to oxidative damage. Aldehyde dehydrogenase (ALDH) activity is a candidate "universal" marker for stem cells. ALDH expression was significantly lower in decidual MSC (DMSC) isolated from preeclamptic (PE) patients. ALDH gene knockdown by siRNA transfection was performed to create a cell culture model of the reduced ALDH expression detected in PE-DMSC. We showed that ALDH activity in DMSC is associated with resistance to hydrogen peroxide (H2O2)-induced toxicity. Our data provide evidence that ALDH expression in DMSC is required for cellular resistance to oxidative stress. Furthermore, candidate ALDH activators were screened and two of the compounds were effective in upregulating ALDH expression. This study provides a proof-of-principle that the restoration of ALDH activity in diseased MSC is a rational basis for a therapeutic strategy to improve MSC resistance to cytotoxic damage.
authors.affiliation: Department of Obstetrics and Gynaecology, Royal Women's Hospital, The University of Melbourne, Parkville, Victoria, 3052, Australia.|Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia.
authors.forename: Gina D
authors.initials: GD
authors.lastname: Kusuma
authors.affiliation: Stem Cells and Regenerative Medicine Department, King Abdullah International Medical Research Centre/ College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City - Ministry of National Guard Health Affairs, P.O. Box 3660, Riyadh 11481, Mail Code 3124, Kingdom of Saudi Arabia.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Abumaree
authors.affiliation: School of Medical Science, Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Southport, Queensland, 9726, Australia.
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Perkins
authors.affiliation: Department of Obstetrics and Gynaecology, Royal Women's Hospital, The University of Melbourne, Parkville, Victoria, 3052, Australia.|Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia.
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brennecke
authors.affiliation: Department of Obstetrics and Gynaecology, Royal Women's Hospital, The University of Melbourne, Parkville, Victoria, 3052, Australia.|Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia.
authors.forename: Bill
authors.initials: B
authors.lastname: Kalionis
mesh_terms: D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019610:Cytoprotection; D003656:Decidua / Q000201:enzymology* / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018384:Oxidative Stress; D011225:Pre-Eclampsia / Q000201:enzymology* / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide; D000444:Aldehyde Dehydrogenase