تاثیر تمرین تناوبی شدید بر بیان ژن پروتئین شوک گرمایی 70 و کاسپاز 3 کاردیومیوسیت‌های موش‌های نر مدل سکته قلبی.

نوع مقاله : مقاله پژوهشی Released under (CC BY-NC 4.0) license I Open Access I

نویسندگان

1 دانشجوی دکتری فیزیولوژی ورزش، گروه تربیت بدنی، دانشکده علوم تربیتی و روان شناسی، اردبیل، ایران

2 استادیار، گروه فیزیولوژی ورزش، دانشکده علوم تربیتی و روان شناسی، دانشگاه محقق اردبیلی، اردبیل، ایران..

3 دانشیار، گروه فیزیولوژی ورزش، دانشکده علوم تربیتی و روان‌شناسی، دانشگاه محقق اردبیلی، اردبیل، ایران.

چکیده

هدف: هدف پژوهش بررسی تاثیر تمرین هوازی تناوبی شدید بر بیان ژن پروتئین شوک گرمایی 70 و کاسپاز 3 کاردیومیوسیت‌های موش‌های نر مدل سکته قلبی بود. روش شناسی: تعداد 30 سر موش صحرائی نر 16 هفته‌ای با وزن 200 تا 250 گرم نژاد ویستار با تزریق درون صفاقی ایزوپروترنول (با دوز 100 میلی‌گرم بر هر کیلوگرم وزن بدن در دو روز متوالی) دچار آنفارکتوس میوکارد (تایید از طریق شاخص‌های آسیب قلبی: CK، LDH و CTnI) شدند و به طور تصادفی در سه گروه (10 سر موش در هر گروه) کنترل سالم، کنترل سکته، سکته + تمرین (HIIT+MI) تقسیم شدند. تمرین HIIT به مدت 8 هفته (5 روز در هفته) شامل 60 دقیقه دویدن تناوبی(4 دقیقه دویدن با شدت 90-85 درصد VO2max و 2 دقیقه ریکاوری فعال با شدت 60 – 50 درصد) انجام شد. بیان ژن‌های HSP70 و کاسپاز 3 کاردیومیوسیت‌ها با استفاده از روش Real-Time PCR انجام شد. داده‌ها با استفاده از روش تحلیل واریانس یک طرفه و آزمون تعقیبی توکی در سطح معنی‌داری 05/0 >  pتحلیل شدند. یافته‌ها: بیان HSP70 کاردیومیوسیت‌ها در موش‌های کنترل مدل MI (سکته کنترل) نسبت به گروه سالم کنترل کمتر بود (001/0=p)؛ با این حال، بیان HSP70 در گروه تمرین HIIT به طور معنی‌داری بیشتر از گروه سکته کنترل و کنترل سالم بود (به ترتیب 001/0=p، 001/0=p). همچنین، بیان کاسپاز 3 در گروه تمرین HIIT به طور معنی داری کمتر از گروه‌های کنترل سالم و کنترل سکته بود (به ترتیب 001/0=p، 001/0=p). نتیجه‌گیری: به نظر می‌رسد تمرین تناوبی شدید در مهار آپوپتوز قلبی ناشی ناشی از سکته موثر باشد. اما، به دلیل محدودیت‌های تحقیق و کمبود شواهد، هنوز نیاز به تحقیقات بیشتر باقی است.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

Effect of high intensity interval training on cardiomyocytes HSP70 and Caspase-3 gene expression levels in myocardial infarction male rat model.

نویسندگان [English]

  • Gabrial Pouzesh Jadidi 1
  • Farnaz Seify 2
  • Lotfali Bolboli 3
  • Amaneh Pourrahim 3
1 PhD Student of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran.
2 Assistant Professor of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran.
3 Associate Professor of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran.
چکیده [English]

Aim: The aim of this study was to investigate the effect of high intensity interval training on cardiomyocytes HSP70 and Caspase-3 gene expression levels in myocardial infarction (MI) male rat model.
 Methods: Thirty male Wistar rats (age: 16 wks, weight: 200 to 250 grams) were randomly divided into three groups of healthy control, MI control and MI training following induction of MI (verified by CK, LDH and CTnI as cardiac injury indices) via intraperitoneal injection of isoproterenol (100 mg/kg.day) within two consecutive days. HIIT was included on eight weeks (5 sessions per week), each session was consisted of 10 bouts of running occasions (each for 4 min) at 85 - 90% of vVo2max with 2 min rest intervals at 50 to 60% of vVO2max. The gene expression levels of HSP70 and Caspase-3 were evaluated using Real-Time PCR method and the data were analyzed using one-way analysis of variance and Tukey post hoc test at the significance level of p <0.05.
Results: Cardiomyocytes HSP70 expression levels was lower in MI control than healthy control counterparts (p=0.001); However, in the HIIT group the expression levels of HSP70 and caspase-3 genes were respectively higher and lower compared to both of healthy control and MI control groups (p=0.001, p=0.001 respectively).
Conclusions:  It seems that HIIT could be efficient for inhibition of MI induced cardiac apoptosis. However further research is needed in this area because of study limitations and lack of similar evidence.

کلیدواژه‌ها [English]

  • HIIT
  • HSP70
  • Myocardial infarction
  • Caspase-3

   

 

This is an open access article distributed under the following Creative Commons license: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

 1.            Song N, Ma J, Meng X-w, Liu H, Wang H, Song S-y, et al. Heat shock protein 70 protects the heart from ischemia/reperfusion injury through inhibition of p38 MAPK signaling. Oxidative Medicine and Cellular Longevity. 2020;2020.
2.             Rentrop KP, Feit F. Reperfusion therapy for acute myocardial infarction: Concepts and controversies from inception to acceptance. American Heart Journal. 2015;170(5):971-80.
3.             Huang K-y, Wang J-n, Zhou Y-y, Wu S-z, Tao L-y, Peng Y-p, et al. Antithrombin III alleviates myocardial ischemia/reperfusion injury by inhibiting excessive autophagy in a phosphoinositide 3-kinase/Akt-dependent manner. Frontiers in Pharmacology. 2019;10:516.
4.             Kennedy D, Jäger R, Mosser DD, Samali A. Regulation of apoptosis by heat shock proteins. IUBMB life. 2014;66(5):327-38.
5.             Liu Y, Lormes W, Wang L, Reissnecker S, Steinacker JM. Different skeletal muscle HSP70 responses to high-intensity strength training and low-intensity endurance training. European journal of applied physiology. 2004;91(2):330-5.
6.             Zhou H, Hou SZ, Luo P, Zeng B, Wang JR, Wong YF, et al. Ginseng protects rodent hearts from acute myocardial ischemia–reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism. Journal of ethnopharmacology. 2011;135(2):287-98.
7.             Ranek MJ, Stachowski MJ, Kirk JA, Willis MS. The role of heat shock proteins and co-chaperones in heart failure. Philosophical Transactions of the Royal Society B: Biological Sciences. 2018;373(1738):20160530.
8.             Zou N, Ao L, Cleveland Jr JC, Yang X, Su X, Cai G-Y, et al. Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion. American Journal of Physiology-Heart and Circulatory Physiology. 2008;294(6):H2805-H13.
9.             Bochaton T, Paccalet A, Jeantet P, Crola Da Silva C, Cartier R, Prieur C, et al. Heat shock protein 70 as a biomarker of clinical outcomes after STEMI. Journal of the American College of Cardiology. 2020;75(1):122-4.
10.          Dybdahl B, Slørdahl S, Waage A, Kierulf P, Espevik T, Sundan A. Myocardial ischaemia and the inflammatory response: release of heat shock protein 70 after myocardial infarction. Heart. 2005;91(3):299-304.
11.          Wu R, Gao W, Dong Z, Su Y, Ji Y, Liao J, et al. Plasma Heat Shock Protein 70 Is Associated With the Onset of Acute Myocardial Infarction and Total Occlusion in Target Vessels. Frontiers in Cardiovascular Medicine. 2021:1153.
12.          Peng W, Zhang Y, Zheng M, Cheng H, Zhu W, Cao C-M, et al. Cardioprotection by CaMKII-δB is mediated by phosphorylation of heat shock factor 1 and subsequent expression of inducible heat shock protein 70. Circulation research. 2010;106(1):102-10.
13.          Zhang C, Liu X, Miao J, Wang S, Wu L, Yan D, et al. Heat shock protein 70 protects cardiomyocytes through suppressing SUMOylation and nucleus translocation of phosphorylated eukaryotic elongation factor 2 during myocardial ischemia and reperfusion. Apoptosis: an international journal on programmed cell death. 2017;22(5):608.
14.          Yao Y-w, Zhang G-h, Zhang Y-y, Li W-d, Wang C-h, Yin C-y, et al. Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB. Cell Stress and Chaperones. 2011;16(3):287-96.
15.          Park YH, Seo JH, Park J-H, Lee HS, Kim K-W. Hsp70 acetylation prevents caspase-dependent/independent apoptosis and autophagic cell death in cancer cells. International journal of oncology. 2017;51(2):573-8.
16.          Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES. Negative regulation of the Apaf-1 apoptosome by Hsp70. Nature cell biology. 2000;2(8):476-83.
17.          Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, et al. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nature cell biology. 2000;2(8):469-75.
18.          Ravagnan L, Gurbuxani S, Susin SA, Maisse C, Daugas E, Zamzami N, et al. Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nature cell biology. 2001;3(9):839-43.
19.          Rahmani M, Sadeghi A, Pourrazi H, Ghiyami SH. The Effect of Eight-Week High Intensity Interval Training (HIIT) and Caffeine Intake On The p38α and hsp70 Protein expression in liver in Diabetic rats induced streptozotocin. Journal of Applied Health Studies in Sport Physiology. 2022;9(1):83-99. [In Persian].
20.          Candé C, Cohen I, Daugas E, Ravagnan L, Larochette N, Zamzami N, et al. Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria. Biochimie. 2002;84(2-3):215-22.
21.          Li C-Y, Lee J-S, Ko Y-G, Kim J-I, Seo J-S. Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation. Journal of Biological Chemistry. 2000;275(33):25665-71.
22.          Li Z, Song Y, Xing R, Yu H, Zhang Y, Li Z, et al. Heat shock protein 70 acts as a potential biomarker for early diagnosis of heart failure. PLoS One. 2013;8(7):e67964.
23.          Alizadeh AM, Isanejad A, Sadighi S, Mardani M, Hassan ZM. High-intensity interval training can modulate the systemic inflammation and HSP70 in the breast cancer: a randomized control trial. Journal of cancer research and clinical oncology. 2019;145(10):2583-93. [In Persian].
24.          Zarali M, Etemad Z, Azizbeigi K, Karimi P. Effect of 8 Weeks of High Intensity Interval Training (HIIT) With and Without Calorie Restriction on Gene Expression of Caspase-3 and Caspase-9 Proteins in Male Rats. Journal of Arak University of Medical Sciences. 2020;23(3):300-13.
25.          Rinaldi B, Corbi G, Boccuti S, Filippelli W, Rengo G, Leosco D, et al. Exercise training affects age-induced changes in SOD and heat shock protein expression in rat heart. Experimental gerontology. 2006;41(8):764-70.
26.          Ogawa K, Sanada K, Machida S, Okutsu M, Suzuki K. Resistance exercise training-induced muscle hypertrophy was associated with reduction of inflammatory markers in elderly women. Mediators of inflammation. 2010;2010.
27.          Walsh R, Koukoulas I, Garnham A, Moseley P, Hargreaves M, Febbraio MA. Exercise increases serum Hsp72 in humans. Cell stress & chaperones. 2001;6(4):386.
28.          Ellison GM, Waring CD, Vicinanza C, Torella D. Physiological cardiac remodelling in response to endurance exercise training: cellular and molecular mechanisms. Heart. 2012;98(1):5-10.
29.          Moeini M, Behpoor N, Tadibi V. The effect of 8 weeks high intensity interval training on the expression of PI3K in the left ventricle and insulin resistance of male Wistar rats with type 2 diabetes. Journal of Practical Studies of Biosciences in Sport. 2020;8(16):48-58. [In Persian].
30.          Wang B, Zhou R, Wang Y, Liu X, Shou X, Yang Y, et al. Effect of high-intensity interval training on cardiac structure and function in rats with acute myocardial infarct. Biomedicine & Pharmacotherapy. 2020;131:110690.
31.          Liao Z, Li D, Chen Y, Li Y, Huang R, Zhu K, et al. Early moderate exercise benefits myocardial infarction healing via improvement of inflammation and ventricular remodelling in rats. Journal of cellular and molecular medicine. 2019;23(12):8328-42.
32.          Zheng H, Xie N, Xu H, Huang J, Xie X, Luo M. Effects of 4 month exercise on left ventricular remodeling and autonomic nervous system in hypertensive patients. Panminerva medica. 2014;58(1):1-7.
33.          Abel ED, Doenst T. Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy. Cardiovascular research. 2011;90(2):234-42.
34.          Rodrigues B, Figueroa DM, Mostarda CT, Heeren MV, Irigoyen M-C, De Angelis KJCd. Maximal exercise test is a useful method for physical capacity and oxygen consumption determination in streptozotocin-diabetic rats. 2007;6(1):38.
35.          Waring CD, Vicinanza C, Papalamprou A, Smith AJ, Purushothaman S, Goldspink DF, et al. The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. European heart journal. 2014;35(39):2722-31.
36.          Schnohr P, O’Keefe JH, Holtermann A, Lavie CJ, Lange P, Jensen GB, et al., editors. Various leisure-time physical activities associated with widely divergent life expectancies: the Copenhagen City Heart Study. Mayo clinic proceedings; 2018: Elsevier.
37.          Cleven L, Krell-Roesch J, Nigg CR, Woll A. The association between physical activity with incident obesity, coronary heart disease, diabetes and hypertension in adults: a systematic review of longitudinal studies published after 2012. BMC public health. 2020;20:1-15.
38.          Benjamin IJ, McMillan DR. Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circulation research. 1998;83(2):117-32.
39.          Paroo Z, Haist JV, Karmazyn M, Noble EG. Exercise improves postischemic cardiac function in males but not females: consequences of a novel sex-specific heat shock protein 70 response. Circulation research. 2002;90(8):911-7.
40.          Melling CJ, Thorp DB, Milne KJ, Krause MP, Noble EG. Exercise-mediated regulation of Hsp70 expression following aerobic exercise training. American Journal of Physiology-Heart and Circulatory Physiology. 2007;293(6):H3692-H8.
41.          Paroo Z, Noble E. Isoproterenol potentiates exercise-induction of Hsp70 in cardiac and skeletal muscle. Cell stress & chaperones. 1999;4(3):199.
42.          Melling CJ, Thorp DB, Noble EG. Regulation of myocardial heat shock protein 70 gene expression following exercise. Journal of molecular and cellular cardiology. 2004;37(4):847-55.
43.          Melling CJ, Krause MP, Noble EG. PKA-mediated ERK1/2 inactivation and hsp70 gene expression following exercise. Journal of molecular and cellular cardiology. 2006;41(5):816-22.
44.          Winzer EB, Woitek F, Linke A. Physical activity in the prevention and treatment of coronary artery disease. Journal of the American Heart Association. 2018;7(4):e007725.
45.          Seo MS, Oh SY, Park MJ, Kim SM, Kim MY, Han SI, et al. Implication of reactive oxygen species, ERK1/2, and p38MAPK in sodium salicylate-induced heat shock protein 72 expression in C6 glioma cells. International journal of molecular medicine. 2005;16(5):841-9.
46.          Sabirzhanov B, Stoica BA, Hanscom M, Piao CS, Faden AI. Over‐expression of HSP70 attenuates caspase‐dependent and caspase‐independent pathways and inhibits neuronal apoptosis. Journal of neurochemistry. 2012;123(4):542-54.
47.          Stankiewicz AR, Lachapelle G, Foo CP, Radicioni SM, Mosser DD. Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation. Journal of Biological Chemistry. 2005;280(46):38729-39.
48.          Lee S-H, Kwon H-M, Kim Y-J, Lee K-M, Kim M, Yoon B-W. Effects of hsp70. 1 gene knockout on the mitochondrial apoptotic pathway after focal cerebral ischemia. Stroke. 2004;35(9):2195-9.
49.          Matsumori Y, Hong SM, Aoyama K, Fan Y, Kayama T, Sheldon RA, et al. Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain injury. Journal of cerebral blood flow & metabolism. 2005;25(7):899-910.
50.          Jiang T, Wang Z, Proctor G, Moskowitz S, Liebman SE, Rogers T, et al. Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. Journal of biological chemistry. 2005;280(37):32317-25.
51.          Kim JY, Barua S, Huang MY, Park J, Yenari MA, Lee JE. Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury. Cells. 2020;9(9).
52.          Krukenberg KA, Street TO, Lavery LA, Agard DA. Conformational dynamics of the molecular chaperone Hsp90. Quarterly reviews of biophysics. 2011;44(2):229-55.
53.          Howard M, Roux J, Lee H, Miyazawa B, Lee J-W, Gartland B, et al. Activation of the stress protein response inhibits the STAT1 signalling pathway and iNOS function in alveolar macrophages: role of Hsp90 and Hsp70. Thorax. 2010;65(4):346-53.
54.          Li J, Soroka J, Buchner J. The Hsp90 chaperone machinery: conformational dynamics and regulation by co-chaperones. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2012;1823(3):624-35.