title: Role of sphingomyelinase in mitochondrial ceramide accumulation during reperfusion.
abstract: Ceramide accumulation in mitochondria has been associated with reperfusion damage, but the underlying mechanisms are not clearly elucidated. In this work we investigate the role of sphingomyelinases in mitochondrial ceramide accumulation, its effect on reactive oxygen species production, as well as on mitochondrial function by using the sphingomyelinase inhibitor, tricyclodecan-9-yl-xanthogenate (D609). Correlation between neutral sphingomyelinase (nSMase) activity and changes in ceramide content were performed in whole tissue and in isolated mitochondria from reperfused hearts. Overall results demonstrated that D609 treatment attenuates cardiac dysfuncion, mitochondrial injury and oxidative stress. Ceramide was accumulated in mitochondria, but not in the microsomal fraction of the ischemic-reperfused (I/R) group. In close association, the activity of nSMase increased, whereas glutathione (GSH) levels diminished in mitochondria after reperfusion. On the other hand, reduction of ceramide levels in mitochondria from I/R+D609 hearts correlated with diminished nSMase activity, coupling of oxidative phosphorylation and with mitochondrial integrity maintenance. These results suggest that mitochondrial nSMase activity contributes to compartmentation and further accumulation of ceramide in mitochondria, deregulating their function during reperfusion.
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology, I. Ch. 14080, Mexico City, Mexico.
authors.forename: I
authors.initials: I
authors.lastname: Ramírez-Camacho
authors.affiliation: Department of Molecular Biology, National Institute of Cardiology, I. Ch. 14080, Mexico City, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Bautista-Pérez
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology, I. Ch. 14080, Mexico City, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Correa
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology, I. Ch. 14080, Mexico City, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Buelna-Chontal
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology, I. Ch. 14080, Mexico City, Mexico.
authors.forename: N G
authors.initials: NG
authors.lastname: Román-Anguiano
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology, I. Ch. 14080, Mexico City, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Medel-Franco
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), University City, 04510 Mexico City, DF, Mexico.
authors.forename: O N
authors.initials: ON
authors.lastname: Medina-Campos
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), University City, 04510 Mexico City, DF, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: Department of Physiology, National Institute of Cardiology, I. Ch., 14080, Mexico City, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Cano-Martínez
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology, I. Ch. 14080, Mexico City, Mexico. Electronic address: azazuetam@yahoo.com.
authors.forename: C
authors.initials: C
authors.lastname: Zazueta
mesh_terms: D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002518:Ceramides / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009636:Norbornanes; D010085:Oxidative Phosphorylation; D051381:Rats; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology
chemical_list: D001952:Bridged-Ring Compounds; D002518:Ceramides; D024101:Mitochondrial Proteins; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D013108:Sphingomyelin Phosphodiesterase; D005978:Glutathione
keywords: Ceramide; Mitochondria; Sphingomyelinase