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Co-enzyme Q10 protects primary chicken myocardial cells from heat stress by upregulating autophagy and suppressing the PI3K/AKT/mTOR pathway

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Cell Stress and Chaperones Aims and scope

Abstract

In this study, we investigated the function of co-enzyme Q10 (Q10) in autophagy of primary chicken myocardial cells during heat stress. Cells were treated with Q10 (1 μΜ, 10 μΜ, and 20 μM) before exposure to heat stress. Pretreatment of chicken myocardial cells with Q10 suppressed the decline in cell viability during heat stress and suppressed the increase in apoptosis during heat stress. Treatment with 20 μM Q10 upregulated autophagy-associated genes during heat stress. The expression of LC3-II was highest in cells treated with 20 μM Q10. Pretreatment with Q10 decreased reactive oxygen species (ROS) levels during heat stress. The number of autophagosomes was significantly increased by 20 μM Q10 treatment, as demonstrated by electron microscopy or monodansylcadaverine (MDC) fluorescence. SQSTM1 accumulation was diminished by Q10 treatment during heat stress, and the number of LC3II puncta was increased. Treatment with 20 μM Q10 also decreased the activation of the PI3K/Akt/mTOR pathway. Our results showed that co-enzyme Q10 can protect primary chicken myocardial cells by upregulating autophagy and suppressing the PI3K/Akt/mTOR pathway during heat stress.

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References

  • Abrahamsen H, Stenmark H, Platta HW (2012) Ubiquitination and phosphorylation of Beclin 1 and its binding partners: tuning class III phosphatidylinositol 3-kinase activity and tumor suppression. FEBS Lett 586:1584–1591

    CAS  PubMed  Google Scholar 

  • Bao ZQ, Liao TT, Yang WR, Wang Y, Luo HY, Wang XZ (2017) Heat stress-induced autophagy promotes lactate secretion in cultured immature boar Sertoli cells by inhibiting apoptosis and driving SLC2A3, LDHA and SLC16A1 expression. Theriogenology. 87:339–348

    CAS  PubMed  Google Scholar 

  • Belviranli M, Okudan N (2019) Effect of coenzyme Q10 alone and in combination with exercise training on oxidative stress biomarkers in rats. Int J Vitam Nutr Res 88:126–136

  • Blázquez AB, Escribano-Romero E, Merino-Ramos T, Saiz JC, Martín-Acebes MA (2014) Stress responses in flavivirus-infected cells: activation of unfolded protein response and autophagy. Front Microbiol 5:266

    PubMed  PubMed Central  Google Scholar 

  • Chen MH, Li XJ, Fan RF, Yang J, Jin X, Hamid S, Xu SW (2018) Cadmium induces BNIP3-dependent autophagy in chicken spleen by modulating miR-33-AMPK axis. Chemosphere. 194:396–402

    CAS  PubMed  Google Scholar 

  • de Andrade Ramos BR, Witkin SS (2016) The influence of oxidative stress and autophagy cross regulation on pregnancy outcome. Cell Stress Chaperones 21:755–762

    PubMed  PubMed Central  Google Scholar 

  • Feng D, Liu L, Zhu Y, Chen Q (2013) Molecular signaling toward mitophagy and its physiological significance. Exp Cell Res 319:1697–1705

    CAS  PubMed  Google Scholar 

  • Flower N, Hartley L, Todkill D, Stranges S, Rees K (2014) Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 12

  • González-Polo RA, Boya P, Pauleau AL, Jalil A, Larochette N, Souquère S, Eskelinen EL, Pierron G, Saftig P, Kroemer G (2005) The apoptosis/autophagy paradox: autophagi cvacuolization before apoptotic death. J Cell Sci 118:3091–3102

    PubMed  Google Scholar 

  • Groulx JF, Khalfaoui T, Benoit YD, Bernatchez G, Carrier JC, Basora N, Beaulieu JF (2012) Autophagy is active in normal colon mucosa. Autophagy. 8:893–902

    CAS  PubMed  PubMed Central  Google Scholar 

  • He X, Lu Z, Ma B, Zhang L, Li J, Jiang Y, Zhou G, Gao F (2019) Chronic heat stress alters hypothalamus integrity, the serum indexes and attenuates expressions of hypothalamic appetite genes in broilers. J Therm Biol 81:110–117

    CAS  PubMed  Google Scholar 

  • Hou X, Hu Z, Xu H, Xu J, Zhang S, Zhong Y, He X, Wang N (2014) Advanced glycation endproducts trigger autophagy in cadiomyocyte via RAGE/PI3K/AKT/mTOR pathway. Cardiovasc Diabetol 13:78

    PubMed  PubMed Central  Google Scholar 

  • Hu YY, Chen X, Li X, Li Z, Diao H, Liu L, Zhang J, Ju J, Wen L, Liu X, Pan Z, Xu C, Hai X, Zhang Y (2019) MicroRNA-1 downregulation induced by carvedilol protects cardiomyocytes against apoptosis by targeting heat shock protein 60. Mol Med Rep 19:327–3536

    Google Scholar 

  • Jin X, Jia TT, Liu RH, Xu SW (2018) The antagonistic effect of selenium on cadmium-induced apoptosis via PPAR-γ/PI3K/Akt pathway in chicken pancreas. J Hazard Mater 357:355–362

    CAS  PubMed  Google Scholar 

  • Jing L, He MT, Chang Y, Mehta SL, He QP, Zhang JZ, Li PA (2015) Coenzyme Q10 protects astrocytes from ROS-induced damage through inhibition of mitochondria-mediated cell death pathway. Int J Biol Sci 11:59–66

    CAS  PubMed  PubMed Central  Google Scholar 

  • Johansen T, Lamark T (2014) Selective autophagy mediated by autophagic adapter proteins. Autophagy. 7:279–296

    Google Scholar 

  • Joung I, Strominger JL, Shin J (1996) Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain. Proc Natl Acad Sci U S A 93:5991–5995

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kalmar B, Greensmith L (2009) Induction of heat shock proteins for protection against oxidative stress. Adv Drug Deliv Rev 61:310–318

    CAS  PubMed  Google Scholar 

  • Kikusato M, Nakamura K, Mikami Y, Mujahid A, Toyomizu M (2016) The suppressive effect of dietary coenzyme Q10 on mitochondrial reactive oxygen species production and oxidative stress in chickens exposed to heat stress. Anim Sci J 87:1244–1251

    CAS  PubMed  Google Scholar 

  • Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 8:445–444

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee E, Koo Y, Ng A, Wei Y, Luby-Phelps K, Juraszek A, Xavier RJ, Cleaver O, Levine B, Amatruda JF (2014) Autophagy is essential for cardiac morphogenesis during vertebrate development. Autophagy. 10:572–587

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li MY, Zhu XL, Zhao BX, Shi L, Wang W, Hu W, Qin SL, Chen BH, Zhou PH, Qiu B, Gao Y, Liu BL (2019) Adrenomedullin alleviates the pyroptosis of Leydig cells by promoting autophagy via the ROS-AMPK-mTOR axis. Cell Death Dis 10:489

    PubMed  PubMed Central  Google Scholar 

  • Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 402:672–676

    CAS  PubMed  Google Scholar 

  • Liang S, Ping Z, Ge J (2017) Coenzyme Q10 regulates antioxidative stress and autophagy in acute myocardial ischemia-reperfusion injury. Oxidative Med Cell Longev 2017:9863181

    Google Scholar 

  • Liu ZF, Ji JJ, Zheng D, Su L, Peng T (2019) Calpain-2 protects against heat stress-induced cardiomyocyte apoptosis and heart dysfunction by blocking p38 mitogen-activated protein kinase activation. J Cell Physiol 234:10761–10770

    CAS  PubMed  Google Scholar 

  • Luo T, Liu G, Ma H, Lu B, Xu H, Wang Y, Wu J, Ge P, Liang J (2014) Inhibition of autophagy via activation of PI3K/Akt pathway contributes to the protection of ginsenoside Rb1 against neuronal death caused by ischemic insults. Int J Mol Sci 15:15426–15442

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lysenko V, Fedorenko G, Fedorenko A, Kirichenko E, Logvinov A, Varduny T (2015) Targeting of organelles into vacuoles and ultrastructure of flower petal epidermis of Petunia hybrida. Braz J Bot 39:327–336

    Google Scholar 

  • Madmani ME, Yusuf Solaiman A, Tamr Agha A, Madmani K, Shahrour Y, Essali Y, Kadro W (2014) Coenzyme Q10 for heart failure. Cochrane Database Syst Rev 6:Cd008684

    Google Scholar 

  • Mehta SL, Manhas N, Raqhubir R (2007) Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev 54:34–66

    CAS  PubMed  Google Scholar 

  • Mizushima N (2004) Methods for monitoring autophagy. Int J Biochem Cell Biol 36:2491–2502

    CAS  PubMed  Google Scholar 

  • Mizushima N (2005) The pleiotropic role of autophagy: from protein metabolism to bactericide. Cell Death Differ 2:1535–1541

    Google Scholar 

  • Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell. 147:728–741

    CAS  PubMed  Google Scholar 

  • Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, George MD, Klionsky DJ, Ohsumi M, Ohsumi Y (1998) A protein conjugation system essential for autophagy. Nature. 395:395–398

    CAS  PubMed  Google Scholar 

  • Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mizushima N, Yoshimori T, Levine B (2010) Methods in mammalian autophagy research. Cell. 140:313–326

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mohamed DI, Khairy E, Tawfek SS, Habib EK, Fetouh MA (2019) Coenzyme Q10 attenuates lung and liver fibrosis via modulation of autophagy in methotrexate treated rat. Biomed Pharmacother 109:892–901

    CAS  PubMed  Google Scholar 

  • N’dri AL, Mignon-Grasteau N, Sellier C, Beaumont M, Tixier-Boichard M (2007) Interactions between the naked neck gene, sex, and fluctuating ambient temperature on heat tolerance, growth, body composition, meat quality, and sensory analysis of slow growing meat type broilers. Livest Sci 110:33–45

    Google Scholar 

  • Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M, Omiya S, Mizote I, Matsumura Y, Asahi M, Nishida K, Hori M, Mizushima N, Otsu K (2007) The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 13:619–624

    CAS  PubMed  Google Scholar 

  • Rauchova H, Drahota Z, Lenaz G (1995) Function of coenzyme Q in the cell: some biochemical and physiological properties. Physiol Res 44:209–216

    CAS  PubMed  Google Scholar 

  • Ravikumar B, Imarisio S, Sarkar S, O’Kane CJ, Rubinsztein DC (2008) Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease. J Cell Sci 121:1649–1660

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rubinsztein DC, Ravikumar B, Acevedoarozena A, Imarisio S, O’Kane CJ, Brown SD (2005) Dyneins, autophagy, aggregation and neurodegeneration. Autophagy. 1:177–178

    CAS  PubMed  Google Scholar 

  • Schmidt N, Ferger B (2001) Neurochemical findings in the MPTP model of Parkinson’s disease. J Neural Transm 108:1263–1282

    CAS  PubMed  Google Scholar 

  • St-Pierre NR, Cobanov B, Schnitkey G (2003) Economic losses from heat stress by US livestock industries. J Dairy Sci 86:E52–E77

    Google Scholar 

  • Tang S, Yin B, Song EB, Cheng HB, Cheng YF, Zhang XH, Bao ED, Hartung J (2016) Aspirin upregulates αB-Crystallin to protect the myocardium against heat stress in broiler chickens. Sci Rep 6:37273

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tanida I, Ueno T, Kominami E (2004) LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 36:2503–2518

    CAS  PubMed  Google Scholar 

  • Tannous P, Zhu H, Johnstone JL, Shelton JM, Rajasekaran NS, Benjamin IJ, Nguyen L, Gerard RD, Levine B, Rothermel BA, Hill JA (2008) Autophagy is an adaptive response in desmin-related cardiomyopathy. Proc Natl Acad Sci U S A 105:9745–9750

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tiwari A, Singh P, Riyazat Khadim S, Singh AK, Singh P, Asthana RK (2019) Role of Ca2+ as protectant under heat stress by regulation of photosynthesis and membrane saturation in Anabaena PCC 7120. Protoplasma. 256:681–691

    CAS  PubMed  Google Scholar 

  • Tsutsui T, Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Ohnishi M, Kinoshita M (2002) Plasma oxidized low-density lipoprotein as a prognostic predictor in patients with chronic congestive heart failure. J Am Coll Cardiol 39:957–962

    CAS  PubMed  Google Scholar 

  • Vanlangenakker N, Vanden Berghe T, Krysko DV, Festjens N, Vandenabeele P (2008) Molecular mechanisms and pathophysiology of necrotic cell death. Curr Mol Med 8:207–220

    CAS  PubMed  Google Scholar 

  • Wang M, Tian Y, Du Y, Sun G, Xu X, Jiang H, Xu H, Meng X, Zhang J, Ding S, Zhang M, Yang M, Sun X (2017) Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90. J Cell Mol Med 21:1870–1880

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang SH, Cheng CY, Chen CJ, Chan HL, Chen HH, Tang PC, Chen CF, Lee YP, Huang SY (2019) Acute heat stress changes protein expression in the testes of a broiler-type strain of Taiwan country chickens. Anim Biotechnol 30:129–145

    CAS  PubMed  Google Scholar 

  • Wu D, Zhang M, Lv YJ, Tang S, Kemper N, Hartung J, Bao ED (2016) Aspirin-induced heat stress resistance in chicken myocardial cells can be suppressed by BAPTA-AM in vitro. Cell Stress Chaperones 21:817–827

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J, Tang S, Song EB, Yin B, Wu D, Bao ED (2017a) Hsp70 expression induced by co-enzyme Q10 protected chicken myocardial cells from damage and apoptosis under in vitro heat stress. Poult Sci 96:1426–1437

    CAS  PubMed  Google Scholar 

  • Xu J, Tang S, Yin B, Sun JR, Song EB, Bao ED (2017b) Co-enzyme Q10 and acetyl salicylic acid enhance Hsp70 expression in primary chicken myocardial cells to protect the cells during heat stress. Mol Cell Biochem 435:73–86

    CAS  PubMed  Google Scholar 

  • Xue R, Wang JX, Yang LX, Liu XJ, Gao Y, Pang YH, Wang YB, Hao JY (2019) Coenzyme Q10 ameliorates pancreatic fibrosis via the ROS-triggered mTOR signaling pathway. Oxid Med Cell Longev 2019:8039694

    PubMed  PubMed Central  Google Scholar 

  • Yang L, Qiu TM, Yao XF, Jiang LP, Wei S, Pei P, Wang ZD, Bai J, Liu XF, Yang G, Liu S, Sun XC (2019) Taurine protects against arsenic trioxide-induced resistance via ROS-autophagy pathway in skeletal muscle. Int J Biochem Cell Biol 112:50–60

    CAS  PubMed  Google Scholar 

  • Zhang XH, Qian Z, Zhu HS, Tang S, Wu D, Zhang M, Kemper N, Hartung J, Bao ED (2016) HSP90 gene expression induced by aspirin is associated with damage remission in a chicken myocardial cell culture exposed to heat stress. Br Poult Sci 5:462–473

    Google Scholar 

  • Zhang Y, Xi X, Mei Y, Zhao X, Zhou L, Ma M, Liu S, Zha X, Yang Y (2019) High-glucose induces retinal pigment epithelium mitochondrial pathways of apoptosis and inhibits mitophagy by regulating ROS/PINK1/Parkin signal pathway. Biomed Pharmacother 111:1315–1325

    CAS  PubMed  Google Scholar 

  • Zhou J, Zhang Y, Qi J, Chi Y, Fan B, Yu JQ, Chen Z (2014) E3 ubiquitin ligase CHIP and NBR1-mediated selective autophagy protect additively against proteotoxicity in plant stress responses. PLoS. Genet 10:e1004116

    PubMed  PubMed Central  Google Scholar 

  • Zhu H, Tannous P, Johnstone JL, Kong Y, Shelton JM, Richardson JA, Le V, Levine B, Rothermel BA, Hill JA (2007) Cardiac autophagy is a maladaptive response to hemodynamic stress. Clin Investig 117:1782–1793

    CAS  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 31602027, 31672520), the Jiangsu Natural Science Foundation of China (grant number BK20160732), the China Postdoctoral Science Foundation (grant number 2016M591860), the Priority Academic Program Development of Jiangsu Higher Education Institutions, Graduate Research, and the Innovation Projects in Jiangsu Province.

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  1. College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, 210095, China

    Jiao Xu, Bei Huang, Shu Tang, Jiarui Sun & Endong Bao

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  1. Jiao Xu
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Correspondence to Endong Bao.

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The study protocol was approved by the Animal Care and Use Committee of Nanjing Agricultural University (Nanjing, China).

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Xu, J., Huang, B., Tang, S. et al. Co-enzyme Q10 protects primary chicken myocardial cells from heat stress by upregulating autophagy and suppressing the PI3K/AKT/mTOR pathway. Cell Stress and Chaperones 24, 1067–1078 (2019). https://doi.org/10.1007/s12192-019-01029-4

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