title: Synthetic liver X receptor agonist T0901317 attenuates high glucose-induced oxidative stress, mitochondrial damage and apoptosis in cardiomyocytes.
abstract: The aim of the present study was to investigate the protective effects of T0901317 (T0), a potent agonist of liver X receptors (LXRs), on high glucose-induced oxidative stress and apoptosis in H9c2 cardiac cells. Exposure of H9c2 cells to high glucose alone, not only caused a significant increase in apoptosis and reactive oxygen species (ROS) generation, but also led to a decrease in mitochondrial membrane potential (ΔΨm), release of cytochrome c, decrease in Bcl-2, increase in Bax expression and the activation of caspase-3, caspase-9, poly (ADP-ribose) polymerase (PARP) and nuclear factor (NF)-κB. However, pretreatment with T0 effectively decreased apoptosis, reduced the levels of ROS, abrogated ΔΨm, inhibited cytochrome c release and NF-κB activation, increased Bcl-2 and decreased Bax expression. In conclusion, our data suggest that T0 exerts protective effects against high glucose-induced apoptosis in H9C2 cardiac muscle cells via inhibition of ROS production, mitochondrial death and NF-κB activation.
authors.affiliation: Department of Pathology, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China; Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang Province 150086, People's Republic of China.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang Province 150086, People's Republic of China; Department of Anatomy, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China.
authors.forename: Yukuan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Medical Imaging, Hongqi Hospital, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang Province 150086, People's Republic of China.
authors.forename: Songbin
authors.initials: S
authors.lastname: Fu
authors.affiliation: Laboratory of Child Nerve Rehabilitation, Jiamusi University, Jiamusi, Heilongjiang Province 154003, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Histology and Embryology, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, Hongqi Hospital, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China.
authors.forename: Xiandong
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Pathology, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China.
authors.forename: Sufen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Anatomy, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China. Electronic address: mdjliuguibo@hotmail.com.
authors.forename: Guibo
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D058065:Diabetic Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000494:pharmacology* / Q000502:physiology; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D000071518:Liver X Receptors; D053078:Membrane Potential, Mitochondrial; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D015533:Transcriptional Activation; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D005947:Glucose; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D016328:NF-kappa B; D057093:Orphan Nuclear Receptors; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
keywords: Apoptosis; Cardiomyocytes; High glucose; Liver X receptor agonist T0901317; Mitochondrial damage