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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

  • Jiao Xu
  • Bei Huang
  • Shu Tang
  • Jiarui Sun
  • Endong BaoEmail author
Original Paper
  • 62 Downloads

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.

Keywords

Co-enzyme Q10 Heat stress Autophagy Myocardial cells Chicken 

Notes

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.

Compliance with ethical standards

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

Conflict of interest

The authors declare that they have no competing interest.

References

  1. 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 586:1584–1591CrossRefGoogle Scholar
  2. 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. 87:339–348CrossRefGoogle Scholar
  3. 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 88:126–136Google Scholar
  4. 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 5:266CrossRefGoogle Scholar
  5. 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. 194:396–402CrossRefGoogle Scholar
  6. de Andrade Ramos BR, Witkin SS (2016) The influence of oxidative stress and autophagy cross regulation on pregnancy outcome. Cell Stress Chaperones 21:755–762CrossRefGoogle Scholar
  7. Feng D, Liu L, Zhu Y, Chen Q (2013) Molecular signaling toward mitophagy and its physiological significance. Exp Cell Res 319:1697–1705CrossRefGoogle Scholar
  8. 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 12Google Scholar
  9. 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 118:3091–3102CrossRefGoogle Scholar
  10. Groulx JF, Khalfaoui T, Benoit YD, Bernatchez G, Carrier JC, Basora N, Beaulieu JF (2012) Autophagy is active in normal colon mucosa. Autophagy. 8:893–902CrossRefGoogle Scholar
  11. 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 81:110–117CrossRefGoogle Scholar
  12. 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 13:78CrossRefGoogle Scholar
  13. 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 19:327–3536Google Scholar
  14. 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 357:355–362CrossRefGoogle Scholar
  15. 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 11:59–66CrossRefGoogle Scholar
  16. Johansen T, Lamark T (2014) Selective autophagy mediated by autophagic adapter proteins. Autophagy. 7:279–296CrossRefGoogle Scholar
  17. 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 93:5991–5995CrossRefGoogle Scholar
  18. 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 19:5720–5728CrossRefGoogle Scholar
  19. Kalmar B, Greensmith L (2009) Induction of heat shock proteins for protection against oxidative stress. Adv Drug Deliv Rev 61:310–318CrossRefGoogle Scholar
  20. 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 87:1244–1251CrossRefGoogle Scholar
  21. 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. 8:445–444CrossRefGoogle Scholar
  22. 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. 10:572–587CrossRefGoogle Scholar
  23. 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 10:489CrossRefGoogle Scholar
  24. 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. 402:672–676CrossRefGoogle Scholar
  25. Liang S, Ping Z, Ge J (2017) Coenzyme Q10 regulates antioxidative stress and autophagy in acute myocardial ischemia-reperfusion injury. Oxidative Med Cell Longev 2017:9863181Google Scholar
  26. 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 234:10761–10770CrossRefGoogle Scholar
  27. 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 15:15426–15442CrossRefGoogle Scholar
  28. 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 39:327–336CrossRefGoogle Scholar
  29. 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:Cd008684Google Scholar
  30. Mehta SL, Manhas N, Raqhubir R (2007) Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev 54:34–66CrossRefGoogle Scholar
  31. Mizushima N (2004) Methods for monitoring autophagy. Int J Biochem Cell Biol 36:2491–2502CrossRefGoogle Scholar
  32. Mizushima N (2005) The pleiotropic role of autophagy: from protein metabolism to bactericide. Cell Death Differ 2:1535–1541CrossRefGoogle Scholar
  33. Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell. 147:728–741CrossRefGoogle Scholar
  34. 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. 395:395–398CrossRefGoogle Scholar
  35. Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075CrossRefGoogle Scholar
  36. Mizushima N, Yoshimori T, Levine B (2010) Methods in mammalian autophagy research. Cell. 140:313–326CrossRefGoogle Scholar
  37. 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 109:892–901CrossRefGoogle Scholar
  38. 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 110:33–45CrossRefGoogle Scholar
  39. 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 13:619–624CrossRefGoogle Scholar
  40. Rauchova H, Drahota Z, Lenaz G (1995) Function of coenzyme Q in the cell: some biochemical and physiological properties. Physiol Res 44:209–216Google Scholar
  41. 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 121:1649–1660CrossRefGoogle Scholar
  42. Rubinsztein DC, Ravikumar B, Acevedoarozena A, Imarisio S, O’Kane CJ, Brown SD (2005) Dyneins, autophagy, aggregation and neurodegeneration. Autophagy. 1:177–178CrossRefGoogle Scholar
  43. Schmidt N, Ferger B (2001) Neurochemical findings in the MPTP model of Parkinson’s disease. J Neural Transm 108:1263–1282CrossRefGoogle Scholar
  44. St-Pierre NR, Cobanov B, Schnitkey G (2003) Economic losses from heat stress by US livestock industries. J Dairy Sci 86:E52–E77CrossRefGoogle Scholar
  45. 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 6:37273CrossRefGoogle Scholar
  46. Tanida I, Ueno T, Kominami E (2004) LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 36:2503–2518CrossRefGoogle Scholar
  47. 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 105:9745–9750CrossRefGoogle Scholar
  48. 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. 256:681–691CrossRefGoogle Scholar
  49. 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 39:957–962CrossRefGoogle Scholar
  50. Vanlangenakker N, Vanden Berghe T, Krysko DV, Festjens N, Vandenabeele P (2008) Molecular mechanisms and pathophysiology of necrotic cell death. Curr Mol Med 8:207–220CrossRefGoogle Scholar
  51. 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 21:1870–1880CrossRefGoogle Scholar
  52. 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 30:129–145CrossRefGoogle Scholar
  53. 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 21:817–827CrossRefGoogle Scholar
  54. 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 96:1426–1437Google Scholar
  55. 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 435:73–86CrossRefGoogle Scholar
  56. 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 2019:8039694CrossRefGoogle Scholar
  57. 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 112:50–60CrossRefGoogle Scholar
  58. 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 5:462–473CrossRefGoogle Scholar
  59. 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 111:1315–1325CrossRefGoogle Scholar
  60. 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:e1004116CrossRefGoogle Scholar
  61. 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 117:1782–1793CrossRefGoogle Scholar

Copyright information

© Cell Stress Society International 2019

Authors and Affiliations

  1. 1.College of Veterinary MedicineNanjing Agricultural UniversityNanjingChina

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