title: Doxycycline protects against ROS-induced mitochondrial fragmentation and ISO-induced heart failure.
abstract: In addition to their anti-bacterial action, tetracyclines also have complex biological effects, including the modification of mitochondrial protein synthesis, metabolism and gene-expression. Long-term clinical studies have been performed using tetracyclines, without significant side effects. Previous studies demonstrated that doxycycline (DOX), a major tetracyclin antibiotic, exerted a protective effect in animal models of heart failure; however, its exact molecular mechanism is still unknown. Here, we provide the first evidence that DOX reduces oxidative stress-induced mitochondrial fragmentation and depolarization in H9c2 cardiomyocytes and beneficially alters the expression of Mfn-2, OPA-1 and Drp-1 -the main regulators of mitochondrial fusion and fission-in our isoproterenol (ISO)-induced heart failure model, ultimately decreasing the severity of heart failure. In mitochondria, oxidative stress causes a shift toward fission which leads to mitochondrial fragmentation and cell death. Protecting mitochondria from oxidative stress, and the regulation of mitochondrial dynamics by drugs that shift the balance toward fusion, could be a novel therapeutic approach for heart failure. On the basis of our findings, we raise the possibility that DOX could be a novel therapeutic agent in the future treatment of heart failure.
authors.affiliation: 1st Department of Medicine, University of Pecs, Pécs, Hungary.|Szentagothai ResearchCenter, University of Pecs, Pécs, Hungary.
authors.forename: Adam
authors.initials: A
authors.lastname: Riba
authors.affiliation: 1st Department of Medicine, University of Pecs, Pécs, Hungary.|Szentagothai ResearchCenter, University of Pecs, Pécs, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Deres
authors.affiliation: 1st Department of Medicine, University of Pecs, Pécs, Hungary.|Szentagothai ResearchCenter, University of Pecs, Pécs, Hungary.
authors.forename: Krisztian
authors.initials: K
authors.lastname: Eros
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pecs, Pécs, Hungary.
authors.forename: Aliz
authors.initials: A
authors.lastname: Szabo
authors.affiliation: 1st Department of Medicine, University of Pecs, Pécs, Hungary.|Szentagothai ResearchCenter, University of Pecs, Pécs, Hungary.
authors.forename: Klara
authors.initials: K
authors.lastname: Magyar
authors.affiliation: Szentagothai ResearchCenter, University of Pecs, Pécs, Hungary.|Department of Biochemistry and Medical Chemistry, University of Pecs, Pécs, Hungary.|MTA-PTE Nuclear-Mitochondrial Interactions Research Group, Pécs, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Sumegi
authors.affiliation: 1st Department of Medicine, University of Pecs, Pécs, Hungary.|Department of Biochemistry and Medical Chemistry, University of Pecs, Pécs, Hungary.|MTA-PTE Nuclear-Mitochondrial Interactions Research Group, Pécs, Hungary.
authors.forename: Kalman
authors.initials: K
authors.lastname: Toth
authors.affiliation: 1st Department of Medicine, University of Pecs, Pécs, Hungary.|Szentagothai ResearchCenter, University of Pecs, Pécs, Hungary.
authors.forename: Robert
authors.initials: R
authors.lastname: Halmosi
authors.affiliation: 1st Department of Medicine, University of Pecs, Pécs, Hungary.|Szentagothai ResearchCenter, University of Pecs, Pécs, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Szabados
mesh_terms: D000318:Adrenergic beta-Agonists / Q000009:adverse effects*; D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology*; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007545:Isoproterenol / Q000009:adverse effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D009124:Muscle Proteins; D017382:Reactive Oxygen Species; D020097:Natriuretic Peptide, Brain; D003094:Collagen; D007545:Isoproterenol; D004318:Doxycycline