:: Volume 32, Issue 3 (Fall 2022) ::
MEDICAL SCIENCES 2022, 32(3): 281-292 Back to browse issues page
The effect of short endurance training on the expression level of PINK-1, Parkin and PGC-1α in the heart of nicotine-sensitized rats
Amir Abbas Lashgari1 , Mohammad Ali Azarbayjani 2, Maghsoud Peeri1 , Mohammad Nasehi3
1- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
2- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran , m_azarbayjani@iauctb.ac.ir
3- Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Abstract:   (1183 Views)
Background: Nicotine alters the expression of various genes in the heart. PINK-1(PTEN-induced kinase1) is the major regulator of cellular mitophagy. Moreover, Parkin is a protein that plays a key role in the process of ubiquitination. Also, PGC-1ὰ (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is the main regulator of mitochondrial biogenesis. On the other hand, exercise has many positive physiological effects on patients suffering from heart failure. In this study, we aimed to investigate the effect of short endurance training on the expression of parkin, PINK1 and PGC- 1ὰ genes in the heart of nicotine-sensitive rats.
Materials and methods: in this study, male Wistar rats weighing approximately 180 to 200 gr were used. The animals received nicotine at dose of 0.21 mg/kg intraperitoneally. Real time PCR technique was used to evaluate the expression of genes.
Results: The results showed that nicotine decreased the expression of PGC-1ὰ gene (p<0.05) and had no effect on other genes (p>0.05). Short-term endurance training slightly increased the expression of all genes that was not statistically significant.
Conclusion: It seems that short-term exercise can reduce the pro–apoptotic and stimulant effects of oxidative stress induced by nicotine. In addition, long-term exercise may potentially induce a significant positive effect on mitophagy-related genes.
 
Keywords: Nicotine, Exercise, Heart, Parkin, PINK-1, PGC-1α
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Semi-pilot: Experimental | Subject: Physiology
Received: 2022/03/10 | Accepted: 2022/09/5 | Published: 2022/09/19
References
1. Goniewicz ML, Delijewski M. Nicotine vaccines to treat tobacco dependence. Hum Vaccin Immunother 2013; 9: 13-25.
2. Benowitz NL. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 2009; 49: 57-71.
3. Korhonen T, Goodwin A, Miesmaa P, Dupuis EA, Kinnunen T. Smoking cessation program with exercise improves cardiovascular disease biomarkers in sedentary women. J Womens Health (Larchmt) 2011; 20: 1051-64.
4. Rigotti NA, Clair C. Managing tobacco use: the neglected cardiovascular disease risk factor. Eur Heart J 2013; 34: 3259-67.
5. Slotkin TA. Fetal nicotine or cocaine exposure: which one is worse? J Pharmacol Exp Ther 1998; 285: 931-45.
6. Xiao D, Xu Z, Huang X, Longo LD, Yang S, Zhang L. Prenatal gender-related nicotine exposure increases blood pressure response to angiotensin II in adult offspring. Hypertension 2008; 51: 1239-47.
7. D'Alessandro A, Boeckelmann I, Hammwhoner M, Goette A. Nicotine, cigarette smoking and cardiac arrhythmia: an overview. Eur J Prev Cardiol 2012; 19: 297-305.
8. Slotkin TA, Skavicus S, Card J, Stadler A, Levin ED, Seidler FJ. Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine. Toxicol Sci 2015; 147: 178-89.
9. Lee SY, Sirieix CM, Nattie E, Li A. Pre- and early postnatal nicotine exposure exacerbates autoresuscitation failure in serotonin-deficient rat neonates. J Physiol 2018; 596: 5977-91.
10. Bozkurt SB, Hakki SS. Nicotine suppresses proliferation and mineralized tissue-associated gene expressions of the cementoblasts. J Periodontol 2019; 91: 800-808.
11. Crotty Alexander LE, Drummond CA, Hepokoski M, Mathew D, Moshensky A, Willeford A, et al. Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice. Am J Physiol Regul Integr Comp Physiol 2018; 314: R834-47.
12. Xiao D, Wang L, Huang X, Li Y, Dasgupta C, Zhang L. Protective Effect of Antenatal Antioxidant on Nicotine-Induced Heart Ischemia-Sensitive Phenotype in Rat Offspring. PLoS One 2016; 11: e0150557.
13. Smith MA Jr, Zhang Y, Polli JR, Wu H, Zhang B, Xiao P, et al. Impacts of chronic low-level nicotine exposure on Caenorhabditis elegans reproduction: identification of novel gene targets. Reprod Toxicol 2013; 40: 69-75.
14. Walsh TG, van den Bosch MTJ, Lewis KE, Williams CM, Poole AW. Loss of the mitochondrial kinase PINK1 does not alter platelet function. Sci Rep 2018; 8: 14377.
15. Koehler CL, Perkins GA, Ellisman MH, Jones DL. Pink1 and Parkin regulate Drosophila intestinal stem cell proliferation during stress and aging. J Cell Biol 2017; 216: 2315-2327.
16. Zhan M, Brooks C, Liu F, Sun L, Dong Z. Mitochondrial dynamics: regulatory mechanisms and emerging role in renal pathophysiology. Kidney Int 2013; 83: 568-81.
17. Springer W, Kahle PJ. Regulation of PINK1-Parkin-mediated mitophagy. Autophagy 2011; 7: 266-78.
18. Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A 2010; 107: 378-83.
19. Toyofuku T, Okamoto Y, Ishikawa T, Sasawatari S, Kumanogoh A. LRRK2 regulates endoplasmic reticulum-mitochondrial tethering through the PERK-mediated ubiquitination pathway. EMBO J 2019: e100875.
20. Passmore LA, Barford D. Getting into position: the catalytic mechanisms of protein ubiquitylation. Biochem J 2004; 379: 513-25.
21. Seirafi M, Kozlov G, Gehring K. Parkin structure and function. FEBS J 2015; 282: 2076-88.
22. Sekine S, Youle RJ. PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol. BMC Biol 2018; 16: 2.
23. Cahill TJ, Leo V, Kelly M, Stockenhuber A, Kennedy NW, Bao L, et al. Resistance of dynamin-related protein 1 oligomers to disassembly impairs mitophagy, resulting in myocardial inflammation and heart failure. J Biol Chem 2016; 291: 25762.
24. Wang B, Nie J, Wu L, Hu Y, Wen Z, Dong L, et al. AMPKalpha2 Protects Against the Development of Heart Failure by Enhancing Mitophagy via PINK1 Phosphorylation. Circ Res 2018; 122: 712-729.
25. Zhang P, Hu X, Xu X, Fassett J, Zhu G, Viollet B, et al. AMP activated protein kinase-alpha2 deficiency exacerbates pressure-overload-induced left ventricular hypertrophy and dysfunction in mice. Hypertension 2008; 52: 918-24.
26. Gustafsson AB, Gottlieb RA. Autophagy in ischemic heart disease. Circ Res 2009; 104: 150-58.
27. Fan G, Chen MJ, Wei J. Involvement of phosphatase and tensin homolog-induced putative kinase 1/Parkin-mediated autophagy in angiotensin II-induced cardiac hypertrophy in C57BL/6 mice. J Int Med Res 2020; 48: 300060519896143>
28. Chen J, Yu W, Ruan Z, Wang S. TUG1/miR-421/PINK1: A potential mechanism for treating myocardial ischemia-reperfusion injury. Int J Cardiol 2019; 292: 197.
29. Zha Z, Wang J, Wang X, Lu M, Guo Y. Involvement of PINK1/Parkin-mediated mitophagy in AGE-induced cardiomyocyte aging. Int J Cardiol 2017; 227: 201-208.
30. Valero, T. Mitochondrial biogenesis: pharmacological approaches. Curr Pharm Des 2014; 20: 5507-509.
31. Dorn GW 2nd, Vega RB, Kelly DP. Mitochondrial biogenesis and dynamics in the developing and diseased heart. Genes Dev 2015; 29: 51-91.
32. Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, et al. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 2002; 418: 797-801.
33. Ciszewski A, Sosnowski C, Beckowski M, Karwowski J. Occlusion of the left anterior descending coronary artery following a negative fractional flow reserve study. Failure or limit of a "gold standard" method? Kardiol Pol 2016; 74: 83.
34. Hua J, Liu Z, Liu Z, An D, Lai W, Zhan Q, et al. Metformin Increases Cardiac Rupture After Myocardial Infarction via the AMPK-MTOR/PGC-1alpha Signaling Pathway in Rats with Acute Myocardial Infarction. Med Sci Monit 2018; 24: 6989-7000.
35. Chang JS, Fernand V, Zhang Y, Shin J, Jun HJ, Joshi Y, et al. NT-PGC-1alpha protein is sufficient to link beta3-adrenergic receptor activation to transcriptional and physiological components of adaptive thermogenesis. J Biol Chem 2012; 287: 9100-11.
36. Kupr B Handschin C. Complex Coordination of Cell Plasticity by a PGC-1alpha-controlled Transcriptional Network in Skeletal Muscle. Front Physiol 2015; 6: 325.
37. Schnyder S, Kupr B, Handschin C. Coregulator-mediated control of skeletal muscle plasticity - A mini-review. Biochimie 2017; 136: 49-54.
38. Finck BN, Kelly DP. PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 2006; 116: 615-22.
39. Chen M, Wang Y, Qu A. PGC-1 alpha accelerates cytosolic Ca2+ clearance without disturbing Ca2+ homeostasis in cardiac myocytes. Biochem Biophys Res Commun 2010; 396: 894-900.
40. Negrao CE, Middlekauff HR, Gomes-Santos IL, Antunes-Correa LM. Effects of exercise training on neurovascular control and skeletal myopathy in systolic heart failure. Am J Physiol Heart Circ Physiol 2015; 308: H792-802.
41. Besnier F, Labrunee M, Pathak A, Pavy-Le Traon A, Gales C, Senard JM, et al. Exercise training-induced modification in autonomic nervous system: An update for cardiac patients. Ann Phys Rehabil Med 2017; 60: 27-35.
42. Sibilitz KL, Berg SK, Tang LH, Risom SS, Gluud C, Lindschou J, et al. Exercise-based cardiac rehabilitation for adults after heart valve surgery. Cochrane Database Syst Rev 2016; 3: CD010876.
43. Balducci S, Leonetti F, Di Mario U, Fallucca F. Is a long-term aerobic plus resistance training program feasible for and effective on metabolic profiles in type 2 diabetic patients? Diabetes Care 2004; 27: 841-2.
44. Uchiyama M, Jin X, Yin E, Shimokawa T, Niimi M. Treadmill exercise induces murine cardiac allograft survival and generates regulatory T cell. Transpl Int 2015; 28: 352-62.
45. Mi C, Qin X, Hou Z, Gao F. Moderate-intensity exercise allows enhanced protection against oxidative stress-induced cardiac dysfunction in spontaneously hypertensive rats. Braz J Med Biol Res 2019; 52: e8009.
46. Cobb, D.B. and Gold, M.R. Treadmill exercise is good for the heart but not to prevent shocks. Heart Rhythm 2017; 14: 1440-41.
47. Hassaan PS, Nassar SZ, Issa Y, Zahran N. Irisin vs. Treadmill Exercise in Post Myocardial Infarction Cardiac Rehabilitation in Rats. Arch Med Res 2019; 50: 44-54.
48. Terada S, Kawanaka K, Goto M, Shimokawa T, Tabata I. Effects of high-intensity intermittent swimming on PGC-1alpha protein expression in rat skeletal muscle. Acta Physiol Scand 2005; 184: 59-65.
49. Little JP, Safdar A, Bishop D, Tarnopolsky MA, Gibala MJ. An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1alpha and activates mitochondrial biogenesis in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 2011; 300: R1303-10.
50. Ozturk N, Olgar Y, Er H, Kucuk M, Ozdemir S. Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations. Cardiol J 2017; 24: 85-93.
51. Short KR. Changes of deleted mtDNA after endurance exercise. Eur J Appl Physiol 2003; 90: 223; author reply 224-5.
52. Kim K, Ahn,N, Jung S. Comparison of endoplasmic reticulum stress and mitochondrial biogenesis responses after 12 weeks of treadmill running and ladder climbing exercises in the cardiac muscle of middle-aged obese rats. Braz J Med Biol Res 2018; 51: e7508.
53. Tam BT, Pei XM, Yung BY, Yip SP, Chan LW, Wong CS, et al. Autophagic Adaptations to Long-term Habitual Exercise in Cardiac Muscle. Int J Sports Med 2015; 36: 526-34.
54. Vettor R, Valerio A, Ragni M, Trevellin E, Granzotto M, Olivieri M, et al. Exercise training boosts eNOS-dependent mitochondrial biogenesis in mouse heart: role in adaptation of glucose metabolism. Am J Physiol Endocrinol Metab 2014; 306: E519-28.
55. Vega RB, Konhilas JP, Kelly DP, Leinwand LA. Molecular Mechanisms Underlying Cardiac Adaptation to Exercise. Cell Metab 2017; 25: 1012-1026.
56. Riehle C, Wende AR, Zhu Y, Oliveira KJ, Pereira RO, Jaishy BP, et al. Insulin receptor substrates are essential for the bioenergetic and hypertrophic response of the heart to exercise training. Mol Cell Biol 2014; 34: 3450-60.
57. Zhao D, Sun Y, Tan Y, Zhang Z, Hou Z, Gao C, et al. Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice. Oxid Med Cell Longev 2018;2018:4079041.
58. Yuan Y, Pan SS. Parkin Mediates Mitophagy to Participate in Cardioprotection Induced by Late Exercise Preconditioning but Bnip3 Does Not. J Cardiovasc Pharmacol 2018; 71: 303-16.
59. Pascual MM, Pastor V, Bernabeu RO. Nicotine-conditioned place preference induced CREB phosphorylation and Fos expression in the adult rat brain. Psychopharmacology (Berl) 2009; 207: 57-71.
60. Reza Zarrindast M, Eslimi Esfahani D, Oryan S, Nasehi M, Torabi Nami M. Effects of dopamine receptor agonist and antagonists on cholestasis-induced anxiolytic-like behaviors in rats. Eur J Pharmacol 2013; 702: 25-31.
61. Virbasius JV, Scarpulla RC. Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Proc Natl Acad Sci U S A 1994; 91: 1309-13.
62. Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 2005; 1: 361-70.
63. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006; 127: 1109-22.
64. Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res 2008; 79: 208-17.
65. Rolle IG, Crivellari I, Caragnano A, Cervellin C, Aleksova A, Cesselli D, et al. Cell Senescence in Cardiac Repair and Failure. Curr Stem Cell Res Ther 2020;15:685-695.
66. Durga Devi T, Babu M, Makinen P, Kaikkonen MU, Heinaniemi M, Laakso H, et al. Aggravated Postinfarct Heart Failure in Type 2 Diabetes Is Associated with Impaired Mitophagy and Exaggerated Inflammasome Activation. Am J Pathol 2017; 187: 2659-2673.
67. Siddall HK, Warrell CE, Davidson SM, Mocanu MM, Yellon DM. Mitochondrial PINK1--a novel cardioprotective kinase? Cardiovasc Drugs Ther 2008; 22: 507-8.
68. Essandoh K, Wang X, Huang W, Deng S, Gardner G, Mu X, et al. Tumor susceptibility gene 101 ameliorates endotoxin-induced cardiac dysfunction by enhancing Parkin-mediated mitophagy. J Biol Chem 2019; 294: 18057-68.
69. Xiong W, Hua J, Liu Z, Cai W, Bai Y, Zhan Q, et al. PTEN induced putative kinase 1 (PINK1) alleviates angiotensin II-induced cardiac injury by ameliorating mitochondrial dysfunction. Int J Cardiol 2018; 266: 198-205.
70. Kubli DA, Zhang X, Lee Y, Hanna RA, Quinsay MN, Nguyen CK, et al. Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J Biol Chem 2013; 288: 915-26.
71. Piepoli MF, Spoletini I, Rosano G. Monitoring functional capacity in heart failure. Eur Heart J 2019; 21: M9-12.
72. Tamargo M, Obokata M, Reddy YNV, Pislaru SV, Lin G, Egbe AC, et al. Functional mitral regurgitation and left atrial myopathy in heart failure with preserved ejection fraction. Eur J Heart Fail 2020;22:489-98.
73. Gan Z, Fu T, Kelly DP, Vega RB. Skeletal muscle mitochondrial remodeling in exercise and diseases. Cell Res 2018; 28: 969-80.
74. Hwang PS, Machek SB, Cardaci TD, Wilburn DT, Kim CS, Suezaki ES, et al. Effects of Pyrroloquinoline Quinone (PQQ) Supplementation on Aerobic Exercise Performance and Indices of Mitochondrial Biogenesis in Untrained Men. J Am Coll Nutr 2019: 1-10.
75. Tao L, Bei Y, Lin S, Zhang H, Zhou Y, Jiang J, et al. Exercise Training Protects Against Acute Myocardial Infarction via Improving Myocardial Energy Metabolism and Mitochondrial Biogenesis. Cell Physiol Biochem 2015; 37: 162-75.
76. Campos JC, Queliconi BB, Bozi LHM, Bechara LRG, Dourado PMM, Andres AM, et al. Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure. Autophagy 2017; 13: 1304-1317.



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