The effect of Diazoxide on norepinephrine-induced cardiac hypertrophy, in vitro

Celal Guven

doi:10.14715/cmb/2018.64.10.8

Issue

Vol. 64 No. 10: Issue 10

Issue Published : August 3, 2018

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

The effect of Diazoxide on norepinephrine-induced cardiac hypertrophy, in vitro

https://doi.org/10.14715/cmb/2018.64.10.8

Celal Guven

The Department of Biophysics, Faculty of Medicine, Nigde Omer Halisdemir University, Nigde, Turkey

Corresponding Author(s) : Celal Guven

cgven@yahoo.com

Cellular and Molecular Biology, Vol. 64 No. 10: Issue 10
Article Published : July 30, 2018

Abstract

Cardiac hypertrophy is associated with mitochondrial dysfunctions, which leads to heart failure if sustained. The aim of present study is to test hypothesis whether activation of mitochondrial KATP channel (mitoKATP) by diazoxide improve mitochondrial membrane potential (MMP) and oxidative stress in an in vitro model of cardiac hypertrophy. Rat cardiomyocytes cell line (H9c2) was used to create four groups as control, diazoxide, hypertrophy, hypertrophy and diazoxide. Norepinephrine was used to induce hypertrophy. Diazoxide and norepinephrine were simultaneously administered. After 24 hours treatment, total oxidant status (TOS), total antioxidant status (TAS) and superoxide dismutase (SOD) activities were measured. MMP and F-actin distribution were analyzed. Hypertrophy significantly elevated TOS level. In addition, diazoxide administration significantly increased TOS level in the normal cell line. There were no significant differences in SOD activity, TAS and oxidative stress index (OSI) between groups. Hypertrophy caused a decrease in MMP and destrupted F-actin. Diazoxide improved MMP and F-actin in mitochondria. Hypertrophy impaired the function and structure of mitochondria. The opening of mitoKATP by diazoxide failed to improve oxidative stress; however, it is effective against mitochondrial damage caused by hypertrophy.

Keywords

Hypertrophy Mitochondrial KATP channel Diazoxide Membrane potential Oxidative stress.

Guven, C. (2018). The effect of Diazoxide on norepinephrine-induced cardiac hypertrophy, in vitro. Cellular and Molecular Biology, 64(10), 50–54. https://doi.org/10.14715/cmb/2018.64.10.8

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References

References
Maulik SK, Kumar S. Oxidative stress and cardiac hypertrophy: a review. Toxicol Mech Methods 2012; 22(5): 359-66.
Rababa'h AM, Guillory AN, Mustafa R, Hijjawi T. Oxidative Stress and Cardiac Remodeling: An Updated Edge. Curr Cardiol Rev 2018; 14(1): 53-9.
Brown DA, Perry JB, Allen ME et al. Expert consensus document: Mitochondrial function as a therapeutic target in heart failure. Nat Rev Cardiol 2017; 14(4): 238-50.
Shimizu I, Minamino T. Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol 2016; 97: 245-62.
Laskowski M, Augustynek B, Kulawiak B et al. What do we not know about mitochondrial potassium channels? Biochim Biophys Acta 2016; 1857(8): 1247-57.
Yamada M. Mitochondrial ATP-sensitive K+ channels, protectors of the heart. J Physiol 2010; 588(Pt 2): 283-6.
Chang JC, Kou SJ, Lin WT, Liu CS. Regulatory role of mitochondria in oxidative stress and atherosclerosis. World J Cardiol 2010; 2(6): 150-9.
Facundo HT, de Paula JG, Kowaltowski AJ. Mitochondrial ATP-sensitive K+ channels prevent oxidative stress, permeability transition and cell death. J Bioenerg Biomembr 2005; 37(2): 75-82.
Gao S, Long CL, Wang RH, Wang H. K(ATP) activation prevents progression of cardiac hypertrophy to failure induced by pressure overload via protecting endothelial function. Cardiovasc Res 2009; 83(3): 444-56.
Malinska D, Mirandola SR, Kunz WS. Mitochondrial potassium channels and reactive oxygen species. FEBS Lett 2010; 584(10): 2043-8.
Zhou GZ, Cao FK, Du SW. The apoptotic pathways in the curcumin analog MHMD-induced lung cancer cell death and the essential role of actin polymerization during apoptosis. Biomed Pharmacother 2015; 71: 128-34.
Peng K, Hu J, Xiao J et al. Mitochondrial ATP-sensitive potassium channel regulates mitochondrial dynamics to participate in neurodegeneration of Parkinson's disease. Biochim Biophys Acta 2018; 1864(4 Pt A): 1086-103.
Xia Y, Rajapurohitam V, Cook MA, Karmazyn M. Inhibition of phenylephrine induced hypertrophy in rat neonatal cardiomyocytes by the mitochondrial KATP channel opener diazoxide. J Mol Cell Cardiol 2004; 37(5): 1063-7.
Youssef N, Campbell S, Barr A et al. Hearts lacking plasma membrane KATP channels display changes in basal aerobic metabolic substrate preference and AMPK activity. Am J Physiol Heart Circ Physiol 2017; 313(3): H469-H78.
Baines CP, Liu GS, Birincioglu M, Critz SD, Cohen MV, Downey JM. Ischemic preconditioning depends on interaction between mitochondrial KATP channels and actin cytoskeleton. Am J Physiol 1999; 276(4 Pt 2): H1361-8.
Foerster F, Braig S, Moser C et al. Targeting the actin cytoskeleton: selective antitumor action via trapping PKCvarepsilon. Cell Death Dis 2014; 5: e1398.
Kang S, Kim K, Noh JY et al. Simvastatin induces the apoptosis of normal vascular smooth muscle through the disruption of actin integrity via the impairment of RhoA/Rac-1 activity. Thromb Haemost 2016; 116(3): 496-505.
Jovanovic S, Jovanovic A. Diadenosine tetraphosphate-gating of cardiac K(ATP) channels requires intact actin cytoskeleton. Naunyn Schmiedebergs Arch Pharmacol 2001; 364(3): 276-80.
Song DK, Ashcroft FM. ATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit. J Biol Chem 2001; 276(10): 7143-9.
Harvey J, Hardy SC, Irving AJ, Ashford ML. Leptin activation of ATP-sensitive K+ (KATP) channels in rat CRI-G1 insulinoma cells involves disruption of the actin cytoskeleton. J Physiol 2000; 527 Pt 1: 95-107.
Akao M, Ohler A, O'Rourke B, Marban E. Mitochondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells. Circ Res 2001; 88(12): 1267-75.
Yang SS, Zheng MX, Xu HC et al. The effect of mitochondrial ATP-sensitive potassium channels on apoptosis of chick embryo cecal cells by Eimeria tenella. Res Vet Sci 2015; 99: 188-95.
Ichinose M, Yonemochi H, Sato T, Saikawa T. Diazoxide triggers cardioprotection against apoptosis induced by oxidative stress. Am J Physiol Heart Circ Physiol 2003; 284(6): H2235-41.
Edamatsu T, Fujieda A, Itoh Y. Phenyl sulfate, indoxyl sulfate and p-cresyl sulfate decrease glutathione level to render cells vulnerable to oxidative stress in renal tubular cells. PLoS One 2018; 13(2): e0193342.
Qiu Y, Tao L, Lei C et al. Downregulating p22phox ameliorates inflammatory response in Angiotensin II-induced oxidative stress by regulating MAPK and NF-kappaB pathways in ARPE-19 cells. Sci Rep 2015; 5: 14362.
Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C. Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci 2013; 14(11): 21525-50.
Niki E. Oxidant-Specific Biomarkers of Oxidative Stress. Association with Atherosclerosis and Implication for Antioxidant Effects. Free Radic Biol Med 2018.
Khan MF, Wang G. Environmental Agents, Oxidative Stress and Autoimmunity. Curr Opin Toxicol 2018; 7: 22-7.
Lv W, Booz GW, Fan F, Wang Y, Roman RJ. Oxidative Stress and Renal Fibrosis: Recent Insights for the Development of Novel Therapeutic Strategies. Front Physiol 2018; 9: 105.
Carroll R, Gant VA, Yellon DM. Mitochondrial K(ATP) channel opening protects a human atrial-derived cell line by a mechanism involving free radical generation. Cardiovasc Res 2001; 51(4): 691-700.
Patel HH, Gross GJ. Diazoxide induced cardioprotection: what comes first, K(ATP) channels or reactive oxygen species? Cardiovasc Res 2001; 51(4): 633-6.
Liang W, Chen M, Zheng D et al. The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway. Cell Physiol Biochem 2017; 41(3): 1020-34.
Liu H, Wang S, Wu Z et al. Glibenclamide, a diabetic drug, prevents acute radiation induced liver injury of mice via up-regulating intracellular ROS and subsequently activating Akt-NF-kappaB pathway. Oncotarget 2017; 8(25): 40568-82.
Lucas AM, Caldas FR, da Silva AP et al. Diazoxide prevents reactive oxygen species and mitochondrial damage, leading to anti-hypertrophic effects. Chem Biol Interact 2017; 261: 50-5.
Browning E, Wang H, Hong N et al. Mechanotransduction drives post ischemic revascularization through K(ATP) channel closure and production of reactive oxygen species. Antioxid Redox Signal 2014; 20(6): 872-86.
Li DL, Ma ZY, Fu ZJ, Ling MY, Yan CZ, Zhang Y. Glibenclamide decreases ATP-induced intracellular calcium transient elevation via inhibiting reactive oxygen species and mitochondrial activity in macrophages. PLoS One 2014; 9(2): e89083.
Heinzel FR, Luo Y, Li X et al. Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice. Circ Res 2005; 97(6): 583-6.
Du X, Xu H, Shi L et al. Activation of ATP-sensitive potassium channels enhances DMT1-mediated iron uptake in SK-N-SH cells in vitro. Sci Rep 2016; 6: 33674.
Forbes RA, Steenbergen C, Murphy E. Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism. Circ Res 2001; 88(8): 802-9.
Liu Y, O'Rourke B. Opening of mitochondrial K(ATP) channels triggers cardioprotection. Are reactive oxygen species involved? Circ Res 2001; 88(8): 750-2.

References

Maulik SK, Kumar S. Oxidative stress and cardiac hypertrophy: a review. Toxicol Mech Methods 2012; 22(5): 359-66.

Rababa'h AM, Guillory AN, Mustafa R, Hijjawi T. Oxidative Stress and Cardiac Remodeling: An Updated Edge. Curr Cardiol Rev 2018; 14(1): 53-9.

Brown DA, Perry JB, Allen ME et al. Expert consensus document: Mitochondrial function as a therapeutic target in heart failure. Nat Rev Cardiol 2017; 14(4): 238-50.

Shimizu I, Minamino T. Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol 2016; 97: 245-62.

Laskowski M, Augustynek B, Kulawiak B et al. What do we not know about mitochondrial potassium channels? Biochim Biophys Acta 2016; 1857(8): 1247-57.

Yamada M. Mitochondrial ATP-sensitive K+ channels, protectors of the heart. J Physiol 2010; 588(Pt 2): 283-6.

Chang JC, Kou SJ, Lin WT, Liu CS. Regulatory role of mitochondria in oxidative stress and atherosclerosis. World J Cardiol 2010; 2(6): 150-9.

Facundo HT, de Paula JG, Kowaltowski AJ. Mitochondrial ATP-sensitive K+ channels prevent oxidative stress, permeability transition and cell death. J Bioenerg Biomembr 2005; 37(2): 75-82.

Gao S, Long CL, Wang RH, Wang H. K(ATP) activation prevents progression of cardiac hypertrophy to failure induced by pressure overload via protecting endothelial function. Cardiovasc Res 2009; 83(3): 444-56.

Malinska D, Mirandola SR, Kunz WS. Mitochondrial potassium channels and reactive oxygen species. FEBS Lett 2010; 584(10): 2043-8.

Zhou GZ, Cao FK, Du SW. The apoptotic pathways in the curcumin analog MHMD-induced lung cancer cell death and the essential role of actin polymerization during apoptosis. Biomed Pharmacother 2015; 71: 128-34.

Peng K, Hu J, Xiao J et al. Mitochondrial ATP-sensitive potassium channel regulates mitochondrial dynamics to participate in neurodegeneration of Parkinson's disease. Biochim Biophys Acta 2018; 1864(4 Pt A): 1086-103.

Xia Y, Rajapurohitam V, Cook MA, Karmazyn M. Inhibition of phenylephrine induced hypertrophy in rat neonatal cardiomyocytes by the mitochondrial KATP channel opener diazoxide. J Mol Cell Cardiol 2004; 37(5): 1063-7.

Youssef N, Campbell S, Barr A et al. Hearts lacking plasma membrane KATP channels display changes in basal aerobic metabolic substrate preference and AMPK activity. Am J Physiol Heart Circ Physiol 2017; 313(3): H469-H78.

Baines CP, Liu GS, Birincioglu M, Critz SD, Cohen MV, Downey JM. Ischemic preconditioning depends on interaction between mitochondrial KATP channels and actin cytoskeleton. Am J Physiol 1999; 276(4 Pt 2): H1361-8.

Foerster F, Braig S, Moser C et al. Targeting the actin cytoskeleton: selective antitumor action via trapping PKCvarepsilon. Cell Death Dis 2014; 5: e1398.

Kang S, Kim K, Noh JY et al. Simvastatin induces the apoptosis of normal vascular smooth muscle through the disruption of actin integrity via the impairment of RhoA/Rac-1 activity. Thromb Haemost 2016; 116(3): 496-505.

Jovanovic S, Jovanovic A. Diadenosine tetraphosphate-gating of cardiac K(ATP) channels requires intact actin cytoskeleton. Naunyn Schmiedebergs Arch Pharmacol 2001; 364(3): 276-80.

Song DK, Ashcroft FM. ATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit. J Biol Chem 2001; 276(10): 7143-9.

Harvey J, Hardy SC, Irving AJ, Ashford ML. Leptin activation of ATP-sensitive K+ (KATP) channels in rat CRI-G1 insulinoma cells involves disruption of the actin cytoskeleton. J Physiol 2000; 527 Pt 1: 95-107.

Akao M, Ohler A, O'Rourke B, Marban E. Mitochondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells. Circ Res 2001; 88(12): 1267-75.

Yang SS, Zheng MX, Xu HC et al. The effect of mitochondrial ATP-sensitive potassium channels on apoptosis of chick embryo cecal cells by Eimeria tenella. Res Vet Sci 2015; 99: 188-95.

Ichinose M, Yonemochi H, Sato T, Saikawa T. Diazoxide triggers cardioprotection against apoptosis induced by oxidative stress. Am J Physiol Heart Circ Physiol 2003; 284(6): H2235-41.

Edamatsu T, Fujieda A, Itoh Y. Phenyl sulfate, indoxyl sulfate and p-cresyl sulfate decrease glutathione level to render cells vulnerable to oxidative stress in renal tubular cells. PLoS One 2018; 13(2): e0193342.

Qiu Y, Tao L, Lei C et al. Downregulating p22phox ameliorates inflammatory response in Angiotensin II-induced oxidative stress by regulating MAPK and NF-kappaB pathways in ARPE-19 cells. Sci Rep 2015; 5: 14362.

Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C. Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci 2013; 14(11): 21525-50.

Niki E. Oxidant-Specific Biomarkers of Oxidative Stress. Association with Atherosclerosis and Implication for Antioxidant Effects. Free Radic Biol Med 2018.

Khan MF, Wang G. Environmental Agents, Oxidative Stress and Autoimmunity. Curr Opin Toxicol 2018; 7: 22-7.

Lv W, Booz GW, Fan F, Wang Y, Roman RJ. Oxidative Stress and Renal Fibrosis: Recent Insights for the Development of Novel Therapeutic Strategies. Front Physiol 2018; 9: 105.

Carroll R, Gant VA, Yellon DM. Mitochondrial K(ATP) channel opening protects a human atrial-derived cell line by a mechanism involving free radical generation. Cardiovasc Res 2001; 51(4): 691-700.

Patel HH, Gross GJ. Diazoxide induced cardioprotection: what comes first, K(ATP) channels or reactive oxygen species? Cardiovasc Res 2001; 51(4): 633-6.

Liang W, Chen M, Zheng D et al. The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway. Cell Physiol Biochem 2017; 41(3): 1020-34.

Liu H, Wang S, Wu Z et al. Glibenclamide, a diabetic drug, prevents acute radiation induced liver injury of mice via up-regulating intracellular ROS and subsequently activating Akt-NF-kappaB pathway. Oncotarget 2017; 8(25): 40568-82.

Lucas AM, Caldas FR, da Silva AP et al. Diazoxide prevents reactive oxygen species and mitochondrial damage, leading to anti-hypertrophic effects. Chem Biol Interact 2017; 261: 50-5.

Browning E, Wang H, Hong N et al. Mechanotransduction drives post ischemic revascularization through K(ATP) channel closure and production of reactive oxygen species. Antioxid Redox Signal 2014; 20(6): 872-86.

Li DL, Ma ZY, Fu ZJ, Ling MY, Yan CZ, Zhang Y. Glibenclamide decreases ATP-induced intracellular calcium transient elevation via inhibiting reactive oxygen species and mitochondrial activity in macrophages. PLoS One 2014; 9(2): e89083.

Heinzel FR, Luo Y, Li X et al. Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice. Circ Res 2005; 97(6): 583-6.

Du X, Xu H, Shi L et al. Activation of ATP-sensitive potassium channels enhances DMT1-mediated iron uptake in SK-N-SH cells in vitro. Sci Rep 2016; 6: 33674.

Forbes RA, Steenbergen C, Murphy E. Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism. Circ Res 2001; 88(8): 802-9.

Liu Y, O'Rourke B. Opening of mitochondrial K(ATP) channels triggers cardioprotection. Are reactive oxygen species involved? Circ Res 2001; 88(8): 750-2.

Author biographies is not available.