Tuncay 2018 MiPschool Tromso C2

From Bioblast
MitoTEMPO ameliorates hyperglycemia induced mitochondrial damage in cardiomyocytes.

Link: MitoEAGLE

Tuncay E, Olgar Y, Turan B (2018)

Event: MiPschool Tromso-Bergen 2018


Reactive oxygen species (ROS) are generated in a wide range of normal physiological conditions. However, ROS production increases in many pathological conditions including cardiovascular diseases, autoimmune diseases and aging. Hyperglycemia and hyperinsulinemia are major contributing factors to oxidative stress increase in mitochondria, which contributes toward the pathogenesis of heart diseases. Experimental studies demonstrated that treatment with MitoTEMPO in hyperglycemic and/or hyperinsulinemic animals improved the cardiac function. Moreover, it has been also shown that an improvement of mitochondrial antioxidant capacity with MitoTEMPO could prevent insulin resistance and preserve vascular and cardiac dysfunctions in animals with either metabolic syndrome or diabetes as well as in aged-animals. MitoTEMPO is a mitochondria-targeted antioxidant and prevents mitochondrial permeability transition pore opening, necrosis and mitochondrial apoptosis after ATP depletion recovery. The mito-TEMPO is a nitroxide conjugated with a triphenylphosphonium moiety that is mitochondria-targeted. Nitroxides are known to be superoxide dismutase (SOD)-mimetics, mito-TEMPO may act as a mitochondrial superoxide scavenger and to protect mitochondria from the hypergiycemia-induced oxidative damage. We used high sucrose diet induced metabolic syndrome (MetS) rats or high glucose incubated H9c2 cells for the experiments. Intracellular free Zn2+, mitochondrial superoxide (MitSOX), mitochondrial membrane potential (MMP) are measured from isolated cardiomyocytes. MetS caused increased intracellar free Zn2+ and MitSOX and depolarization of MMP. Incubation MetS cardiomyoxytes with MitoTempo for 2 hours prevented increase of intracellular free Zn2+ and MitSOX production and protected MMP depolarization. Determine the role of MitoTempo on sarco(endo)plasmicreticulum/ mitochondria coupling, we measured mitofusin-protein Mfn-1/2, a mitochondrial fission protein, Fis-1 in isolated cardiomyocytes. Our data demonstrated that MitoTempo prevented mitochondrial fission in MetS rats. Overall, recent data suggest that new therapeutic approaches directly targeting the mitochondria are very important in pathological conditions, particularly under insulin resistance, for heart dysfunction.

β€’ Bioblast editor: Beno M, Plangger M

Affiliations and Support

Dept Biophysics, Ankara Univ, Fac Medicine, Ankara, Turkey

This project supported by TUBITAK SBAG.

Labels: MiParea: mt-Medicine, Pharmacology;toxicology  Pathology: Cardiovascular, Diabetes 

Organism: Rat  Tissue;cell: Heart 

Event: C2, Oral 

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