title: Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications.
abstract: Cellular responses to high glucose are numerous and varied but ultimately result in functional changes and, often, cell death. High glucose induces oxidative and nitrosative stress in many cell types causing the generation of species such as superoxide, nitric oxide and peroxynitrite and their derivatives. The role of these species in high glucose-mediated apoptotic cell death is relevant to the complications of diabetes such as neuropathy, nephropathy and cardiovascular disease. High glucose causes activation of several proteins involved in apoptotic cell death, including members of the caspase and Bcl-2 families. These events and the relationship between high glucose-induced oxidative stress and apoptosis are discussed here with reference to additional regulators of apoptosis such as the mitogen-activated protein kinases (MAPKs) and cell-cycle regulators.
authors.affiliation: Centre for Experimental Medicine, Nephrology and Critical Care, William Harvey Research Institute, St. Bartholomew's and Royal London School of Medicine and Dentistry, Queen Mary, University of London, EC1M 6BQ London, UK. d.a.allen@qmul.ac.uk
authors.forename: David A
authors.initials: DA
authors.lastname: Allen
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Yaqoob
authors.forename: Steven M
authors.initials: SM
authors.lastname: Harwood
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage; D048909:Diabetes Complications / Q000209:etiology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D008928:Mitochondria / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; D005947:Glucose