title: Analysis of mtDNA, miR-155 and BACH1 expression in hearts from donors with and without Down syndrome.
abstract: Cancer patients with Down syndrome (DS) are at increased risk for anthracycline-related cardiotoxicity. Mitochondrial DNA (mtDNA) alterations in hearts with-DS may contribute to anthracycline-related cardiotoxicity. Cardiac mtDNA and the mtDNA(4977) deletion were quantitated in samples with- (n = 11) and without-DS (n = 31). Samples with-DS showed 30% lower mtDNA (DS(MT-ND1/18Sratio): 1.48 ± 0.72 versus non-DS(MT-ND1/18Sratio): 2.10 ± 1.59; p = 0.647) and 30% higher frequency of the mtDNA(4977) deletion (DS(% frequency mtDNA(4977)) deletion: 0.0086 ± 0.0166 versus non-DS(% frequency mtDNA(4977)) deletion: 0.0066 ± 0.0124, p = 0.514) than samples without-DS. The BACH1 and microRNA-155 (miR-155) genes are located in chromosome 21, and their products have demonstrated roles during oxidative stress. BACH1 and miR-155 expression did not differ in hearts with- and without-DS. An association between BACH1 and miR-155 expression was detected in hearts without-DS, suggesting alterations between BACH1-miR-155 interactions in the DS settings.
authors.affiliation: a Department of Pharmaceutical Sciences, University at Buffalo , The State University of New York , Buffalo , NY , USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Hefti
authors.affiliation: a Department of Pharmaceutical Sciences, University at Buffalo , The State University of New York , Buffalo , NY , USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Quiñones-Lombraña
authors.affiliation: a Department of Pharmaceutical Sciences, University at Buffalo , The State University of New York , Buffalo , NY , USA.
authors.forename: Almedina
authors.initials: A
authors.lastname: Redzematovic
authors.affiliation: a Department of Pharmaceutical Sciences, University at Buffalo , The State University of New York , Buffalo , NY , USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hui
authors.affiliation: a Department of Pharmaceutical Sciences, University at Buffalo , The State University of New York , Buffalo , NY , USA.
authors.forename: Javier G
authors.initials: JG
authors.lastname: Blanco
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D066126:Cardiotoxicity; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D004272:DNA, Mitochondrial / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D050259:Genes, Mitochondrial; D006331:Heart Diseases / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D010865:Pilot Projects; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D004272:DNA, Mitochondrial; D051856:Fanconi Anemia Complementation Group Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Anthracycline-related cardiotoxicity; Down syndrome; mitochondrial DNA; oxidative stress