title: Cardiac mitochondrial dysfunction during hyperglycemia--the role of oxidative stress and p66Shc signaling.
abstract: Diabetes mellitus is a chronic disease caused by a deficiency in the production of insulin and/or by the effects of insulin resistance. Insulin deficiency leads to hyperglycemia which is the major initiator of diabetic cardiovascular complications escalating with time and driven by many complex biochemical and molecular processes. Four hypotheses, which propose mechanisms of diabetes-associated pathophysiology, are currently considered. Cardiovascular impairment may be caused by an increase in polyol pathway flux, by intracellular advanced glycation end-products formation or increased flux through the hexosamine pathway. The latter of these mechanisms involves activation of the protein kinase C. Cellular and mitochondrial metabolism alterations observed in the course of diabetes are partially associated with an excessive production of reactive oxygen species (ROS). Among many processes and factors involved in ROS production, the 66 kDa isoform of the growth factor adaptor shc (p66Shc protein) is of particular interest. This protein plays a key role in the control of mitochondria-dependent oxidative balance thus it involvement in diabetic complications and other oxidative stress based pathologies is recently intensively studied. In this review we summarize the current understanding of hyperglycemia induced cardiac mitochondrial dysfunction with an emphasis on the oxidative stress and p66Shc protein. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.
authors: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
authors: Catia V
authors: CV
authors: Diogo
authors: Jan M
authors: JM
authors: Suski
authors: Magdalena
authors: M
authors: Lebiedzinska
authors: Agnieszka
authors: A
authors: Karkucinska-Wieckowska
authors: Aleksandra
authors: A
authors: Wojtala
authors: Maciej
authors: M
authors: Pronicki
authors: Jerzy
authors: J
authors: Duszynski
authors: Paolo
authors: P
authors: Pinton
authors: Piero
authors: P
authors: Portincasa
authors: Paulo J
authors: PJ
authors: Oliveira
authors: Mariusz R
authors: MR
authors: Wieckowski
mesh_terms: D000818:Animals; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D055765:Shc Signaling Adaptor Proteins