title: Scavenging system efficiency is crucial for cell resistance to ROS-mediated methylglyoxal injury.
abstract: Methylglyoxal is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Recent research indicates that methylglyoxal is a potent growth inhibitor and genotoxic agent. The antiproliferative activity of methylglyoxal has been investigated for pharmacological application in cancer chemotherapy. However, various cells are not equally sensitive to methylglyoxal toxicity. Therefore, it would be important to establish the cellular factors responsible for the different cell-type specific response to methylglyoxal injury, in order to avoid the risk of failure of a therapy based on increasing the intracellular level of methylglyoxal. To this purpose, we comparatively evaluated the signaling transduction pathway elicited by methylglyoxal in human glioblastoma (ADF) and neuroblastoma (SH-SY 5Y) cells. Results show that methylglyoxal causes early and extensive reactive oxygen species generation in both cell lines. However, SH-SY 5Y cells show higher sensitivity to methylglyoxal challenge due to a defective antioxidant and detoxifying ability that, preventing these cells from an efficient scavenging action, elicits extensive caspase-9 dependent apoptosis. These data emphasize the pivotal role of antioxidant and detoxifying systems in determining the grade of sensitivity of cells to methylglyoxal.
authors.affiliation: Department of Basic and Applied Biology, Faculty of Science, L'Aquila University, L'Aquila, Italy. fernanda.amicarelli@univaq.it
authors.forename: Fernanda
authors.initials: F
authors.lastname: Amicarelli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Colafarina
authors.forename: Franca
authors.initials: F
authors.lastname: Cattani
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cimini
authors.forename: Carmine
authors.initials: C
authors.lastname: Di Ilio
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Ceru
authors.forename: Michele
authors.initials: M
authors.lastname: Miranda
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016166:Free Radical Scavengers; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005981:Glutathione Synthase / Q000378:metabolism; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D011765:Pyruvaldehyde / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D020169:Caspases; D002374:Catalase; D016166:Free Radical Scavengers; D005979:Glutathione Peroxidase; D005981:Glutathione Synthase; D007791:Lactoylglutathione Lyase; D016328:NF-kappa B; D011765:Pyruvaldehyde; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D013482:Superoxide Dismutase; D013869:Thiolester Hydrolases; D014157:Transcription Factors; D000099301:Hydroxyacylglutathione Hydrolase