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Alterations of housekeeping proteins in human aged and diseased hearts

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Abstract

Pathological remodeling includes alterations of ion channel function and calcium homeostasis and ultimately cardiac maladaptive function during the process of disease development. Biochemical assays are important approaches for assessing protein abundance and post-translational modification of ion channels. Several housekeeping proteins are commonly used as internal controls to minimize loading variabilities in immunoblotting protein assays. Yet, emerging evidence suggests that some housekeeping proteins may be abnormally altered under certain pathological conditions. However, alterations of housekeeping proteins in aged and diseased human hearts remain unclear. In the current study, immunoblotting was applied to measure three commonly used housekeeping proteins (β-actin, calsequestrin, and GAPDH) in well-procured human right atria (RA) and left ventricles (LV) from diabetic, heart failure, and aged human organ donors. Linear regression analysis suggested that the amounts of linearly loaded total proteins and quantified intensity of total proteins from either Ponceau S (PS) blot-stained or Coomassie Blue (CB) gel-stained images were highly correlated. Thus, all immunoblotting data were normalized with quantitative CB or PS data to calibrate potential loading variabilities. In the human heart, β-actin was reduced in diabetic RA and LV, while GAPDH was altered in aged and diabetic RA but not LV. Calsequestrin, an important Ca2+ regulatory protein, was significantly changed in aged, diabetic, and ischemic failing hearts. Intriguingly, expression levels of all three proteins were unchanged in non-ischemic failing human LV. Overall, alterations of human housekeeping proteins are heart chamber specific and disease context dependent. The choice of immunoblotting loading controls should be carefully evaluated. Usage of CB or PS total protein analysis could be a viable alternative approach for some complicated pathological specimens.

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References

  1. Ai X, Pogwizd SM (2005) Connexin 43 downregulation and dephosphorylation in nonischemic heart failure is associated with enhanced colocalized protein phosphatase type 2A. Circ Res 96:54–63. https://doi.org/10.1161/01.RES.0000152325.07495.5a

    Article  CAS  PubMed  Google Scholar 

  2. Ai X, Curran JW, Shannon TR, Bers DM, Pogwizd SM (2005) Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure. Circ Res 97:1314–1322. https://doi.org/10.1161/01.RES.0000194329.41863.89

    Article  CAS  PubMed  Google Scholar 

  3. Ai X, Zhao W, Pogwizd SM (2010) Connexin43 knockdown or overexpression modulates cell coupling in control and failing rabbit left ventricular myocytes. Cardiovasc Res 85:751–762. https://doi.org/10.1093/cvr/cvp353

    Article  CAS  PubMed  Google Scholar 

  4. Ai X, Jiang A, Ke Y, Solaro RJ, Pogwizd SM (2011) Enhanced activation of p21-activated kinase 1 in heart failure contributes to dephosphorylation of connexin 43. Cardiovasc Res 92:106–114. https://doi.org/10.1093/cvr/cvr163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Banerjee I, Yekkala K, Borg TK, Baudino TA (2006) Dynamic interactions between myocytes, fibroblasts, and extracellular matrix. Ann N Y Acad Sci 1080:76–84. https://doi.org/10.1196/annals.1380.007

    Article  CAS  PubMed  Google Scholar 

  6. Benjamin EJ, Levy D, Vaziri SM, D’Agostino RB, Belanger AJ, Wolf PA (1994) Independent risk factors for atrial fibrillation in a population-based cohort. The framingham heart study. JAMA 271:840–844

    Article  CAS  Google Scholar 

  7. Bidasee KR, Nallani K, Besch HR Jr, Dincer UD (2003) Streptozotocin-induced diabetes increases disulfide bond formation on cardiac ryanodine receptor (RyR2). J Pharmacol Exp Ther 305:989–998. https://doi.org/10.1124/jpet.102.046201

    Article  CAS  PubMed  Google Scholar 

  8. Bunnell TM, Burbach BJ, Shimizu Y, Ervasti JM (2011) Beta-actin specifically controls cell growth, migration, and the G-actin pool. Mol Biol Cell 22:4047–4058. https://doi.org/10.1091/mbc.E11-06-0582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dennis-Sykes CA, Miller WJ, McAleer WJ (1985) A quantitative Western blot method for protein measurement. J Biol Stand 13:309–314. https://doi.org/10.1016/s0092-1157(85)80044-5

    Article  CAS  PubMed  Google Scholar 

  10. Deshpande ADH-HM, Schootman M (2008) Epidemiology of diabetes and diabetes-related complications. Phys Ther 88:1254–1264. https://doi.org/10.2522/ptj.20080020

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dittmer A, Dittmer J (2006) Beta-actin is not a reliable loading control in Western blot analysis. Electrophoresis 27:2844–2845. https://doi.org/10.1002/elps.200500785

    Article  CAS  PubMed  Google Scholar 

  12. Eaton SL, Roche SL, Llavero Hurtado M, Oldknow KJ, Farquharson C, Gillingwater TH, Wishart TM (2013) Total protein analysis as a reliable loading control for quantitative fluorescent Western blotting. PLoS One 8:e72457. https://doi.org/10.1371/journal.pone.0072457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Faggioni M, Knollmann BC (2012) Calsequestrin 2 and arrhythmias. Am J Physiol Heart Circ Physiol 302:H1250–H1260. https://doi.org/10.1152/ajpheart.00779.2011

    Article  CAS  PubMed  Google Scholar 

  14. Ferguson RE, Carroll HP, Harris A, Maher ER, Selby PJ, Banks RE (2005) Housekeeping proteins: a preliminary study illustrating some limitations as useful references in protein expression studies. Proteomics 5:566–571. https://doi.org/10.1002/pmic.200400941

    Article  CAS  PubMed  Google Scholar 

  15. Franklin JL, Amsler MO, Messina JL (2016) Prenylation differentially inhibits insulin-dependent immediate early gene mRNA expression. Biochem Biophys Res Commun 474:594–598. https://doi.org/10.1016/j.bbrc.2016.04.067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gao X, Wu X, Yan J, Zhang J, Zhao W, DeMarco D, Zhang Y, Bakhos M, Mignery G, Sun J, Li Z, Fill M, Ai X (2018) Transcriptional regulation of stress kinase JNK2 in pro-arrhythmic CaMKIIdelta expression in the aged atrium. Cardiovasc Res 114:737–746. https://doi.org/10.1093/cvr/cvy011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE (2001) Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 285:2370–2375. https://doi.org/10.1001/jama.285.18.2370

    Article  CAS  PubMed  Google Scholar 

  18. Greer S, Honeywell R, Geletu M, Arulanandam R, Raptis L (2010) Housekeeping genes; expression levels may change with density of cultured cells. J Immunol Methods 355:76–79. https://doi.org/10.1016/j.jim.2010.02.006

    Article  CAS  PubMed  Google Scholar 

  19. Gyorke I, Hester N, Jones LR, Gyorke S (2004) The role of calsequestrin, triadin, and junctin in conferring cardiac ryanodine receptor responsiveness to luminal calcium. Biophys J 86:2121–2128. https://doi.org/10.1016/S0006-3495(04)74271-X

    Article  PubMed  PubMed Central  Google Scholar 

  20. Herraiz-Martinez A, Alvarez-Garcia J, Llach A, Molina CE, Fernandes J, Ferrero-Gregori A, Rodriguez C, Vallmitjana A, Benitez R, Padro JM, Martinez-Gonzalez J, Cinca J, Hove-Madsen L (2015) Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes. Cardiovasc Res 106:76–86. https://doi.org/10.1093/cvr/cvv046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jones LR, Suzuki YJ, Wang W, Kobayashi YM, Ramesh V, Franzini-Armstrong C, Cleemann L, Morad M (1998) Regulation of Ca2+ signaling in transgenic mouse cardiac myocytes overexpressing calsequestrin. J Clin Invest 101:1385–1393. https://doi.org/10.1172/JCI1362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Juhaszova M, Rabuel C, Zorov DB, Lakatta EG, Sollott SJ (2005) Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res 66:233–244. https://doi.org/10.1016/j.cardiores.2004.12.020

    Article  CAS  PubMed  Google Scholar 

  23. Karin M (2005) Inflammation-activated protein kinases as targets for drug development. Proc Am Thorac Soc 2:386–390; discussion 394-385. https://doi.org/10.1513/pats.200504-034SR

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Klein D, Kern RM, Sokol RZ (1995) A method for quantification and correction of proteins after transfer to immobilization membranes. Biochem Mol Biol Int 36:59–66

    CAS  PubMed  Google Scholar 

  25. Li SY, Du M, Dolence EK, Fang CX, Mayer GE, Ceylan-Isik AF, LaCour KH, Yang X, Wilbert CJ, Sreejayan N, Ren J (2005) Aging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification. Aging Cell 4:57–64. https://doi.org/10.1111/j.1474-9728.2005.00146.x

    Article  CAS  PubMed  Google Scholar 

  26. Lowe DA, Degens H, Chen KD, Alway SE (2000) Glyceraldehyde-3-phosphate dehydrogenase varies with age in glycolytic muscles of rats. J Gerontol A Biol Sci Med Sci 55:B160–B164. https://doi.org/10.1093/gerona/55.3.b160

    Article  CAS  PubMed  Google Scholar 

  27. Luitse MJA, Biessels GJ, Rutten GEHM, Kappelle LJ (2012) Diabetes, hyperglycaemia, and acute ischaemic stroke. Lancet Neurol 11:261–271. https://doi.org/10.1016/s1474-4422(12)70005-4

    Article  PubMed  Google Scholar 

  28. McLoughlin KJ, Pedrini E, MacMahon M, Guduric-Fuchs J, Medina RJ (2019) Selection of a real-time PCR housekeeping gene panel in human endothelial colony forming cells for cellular senescence studies. Front Med (Lausanne) 6:33. https://doi.org/10.3389/fmed.2019.00033

    Article  Google Scholar 

  29. Meyer M, Schillinger W, Pieske B, Holubarsch C, Heilmann C, Posival H, Kuwajima G, Mikoshiba K, Just H, Hasenfuss G et al (1995) Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy. Circulation 92:778–784. https://doi.org/10.1161/01.cir.92.4.778

    Article  CAS  PubMed  Google Scholar 

  30. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward JB, Tsang TS (2006) Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 114:119–125. https://doi.org/10.1161/CIRCULATIONAHA.105.595140

    Article  PubMed  Google Scholar 

  31. Onyia JE, Halladay DL, Messina JL (1995) One of three CCArGG box/serum response elements of the beta-actin gene is an insulin-responsive element. Endocrinology 136:306–315. https://doi.org/10.1210/endo.136.1.7828546

    Article  CAS  PubMed  Google Scholar 

  32. Peravali R, Gunnels L, Alleboina S, Gerling IC, Dokun AO (2019) Type 1 diabetes alters ischemia-induced gene expression. J Clin Transl Endocrinol 15:19–24. https://doi.org/10.1016/j.jcte.2018.11.003

    Article  PubMed  Google Scholar 

  33. Peravali R, Gunnels L, Dhanabalan K, Ariganjoye F, Gerling IC, Dokun AO (2019) In experimental peripheral arterial disease, type 2 diabetes alters post-ischemic gene expression. J Clin Transl Endocrinol 17:100199. https://doi.org/10.1016/j.jcte.2019.100199

    Article  PubMed  PubMed Central  Google Scholar 

  34. Pires RH, Shree N, Manu E, Guzniczak E, Otto O (2019) Cardiomyocyte mechanodynamics under conditions of actin remodelling. Philos Trans R Soc Lond Ser B Biol Sci 374:20190081. https://doi.org/10.1098/rstb.2019.0081

    Article  CAS  Google Scholar 

  35. Rich MW (2009) Epidemiology of atrial fibrillation. J Interv Card Electrophysiol 25:3–8. https://doi.org/10.1007/s10840-008-9337-8

    Article  PubMed  Google Scholar 

  36. Rose BA, Force T, Wang Y (2010) Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale. Physiol Rev 90:1507–1546. https://doi.org/10.1152/physrev.00054.2009

    Article  CAS  PubMed  Google Scholar 

  37. Rybicki EP, von Wechmar MB (1982) Enzyme-assisted immune detection of plant virus proteins electroblotted onto nitrocellulose paper. J Virol Methods 5:267–278. https://doi.org/10.1016/0166-0934(82)90017-9

    Article  CAS  PubMed  Google Scholar 

  38. Said HM, Polat B, Hagemann C, Anacker J, Flentje M, Vordermark D (2009) Absence of GAPDH regulation in tumor-cells of different origin under hypoxic conditions in - vitro. BMC Res Notes 2:8. https://doi.org/10.1186/1756-0500-2-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sarfraz A, Tunio NJO, Ala’Aldeen DAA, Wooldridge KG, Turner DPJ (2010) The role of glyceraldehyde 3-phosphate dehydrogenase (GapA-1) in Neisseria meningitidis adherence to human cells. BMC Microbiol 10:280

    Article  Google Scholar 

  40. Schillinger WMM, Kuwajima G, Mikoshiba K, Just H, Hasenfuss G (1996) Unaltered ryanodine receptor protein levels in ischemic cardiomyopathy. Mol Cell Biochem 160/161:297–302

    Article  CAS  Google Scholar 

  41. Scriven DR, Dan P, Moore ED (2000) Distribution of proteins implicated in excitation-contraction coupling in rat ventricular myocytes. Biophys J 79:2682–2691. https://doi.org/10.1016/S0006-3495(00)76506-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shah AD, Langenberg C, Rapsomaniki E, Denaxas S, Pujades-Rodriguez M, Gale CP, Deanfield J, Smeeth L, Timmis A, Hemingway H (2015) Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people. Lancet Diabetes Endocrinol 3:105–113. https://doi.org/10.1016/s2213-8587(14)70219-0

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tarze A, Deniaud A, Le Bras M, Maillier E, Molle D, Larochette N, Zamzami N, Jan G, Kroemer G, Brenner C (2007) GAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane permeabilization. Oncogene 26:2606–2620. https://doi.org/10.1038/sj.onc.1210074

    Article  CAS  PubMed  Google Scholar 

  44. Taylor SC, Posch A (2014) The design of a quantitative western blot experiment. Biomed Res Int 2014:361590–361598. https://doi.org/10.1155/2014/361590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Terentyev D, Viatchenko-Karpinski S, Vedamoorthyrao S, Oduru S, Gyorke I, Williams SC, Gyorke S (2007) Protein protein interactions between triadin and calsequestrin are involved in modulation of sarcoplasmic reticulum calcium release in cardiac myocytes. J Physiol 583:71–80. https://doi.org/10.1113/jphysiol.2007.136879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Timaru-Kast R, Herbig EL, Luh C, Engelhard K, Thal SC (2015) Influence of age on cerebral housekeeping gene expression for normalization of quantitative polymerase chain reaction after acute brain injury in mice. J Neurotrauma 32:1777–1788. https://doi.org/10.1089/neu.2014.3784

    Article  PubMed  Google Scholar 

  47. Touchberry CD, Wacker MJ, Richmond SR, Whitman SA, Godard MP (2006) Age-related changes in relative expression of real-time PCR housekeeping genes in human skeletal muscle. J Biomol Tech 17:157–162

    PubMed  PubMed Central  Google Scholar 

  48. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 76:4350–4354. https://doi.org/10.1073/pnas.76.9.4350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Veres-Szekely A, Pap D, Sziksz E, Javorszky E, Rokonay R, Lippai R, Tory K, Fekete A, Tulassay T, Szabo AJ, Vannay A (2017) Selective measurement of alpha smooth muscle actin: why beta-actin can not be used as a housekeeping gene when tissue fibrosis occurs. BMC Mol Biol 18:12. https://doi.org/10.1186/s12867-017-0089-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Shay CM, Spartano NL, Stokes A, Tirschwell DL, VanWagner LB, Tsao CW, American Heart Association Council on E, Prevention Statistics C, Stroke Statistics S (2020) Heart Disease and Stroke Statistics-2020 Update: a report from the American Heart Association. Circulation 141:e139–e596. https://doi.org/10.1161/CIR.0000000000000757

    Article  PubMed  Google Scholar 

  51. Voigt N, Heijman J, Wang Q, Chiang DY, Li N, Karck M, Wehrens XHT, Nattel S, Dobrev D (2014) Cellular and molecular mechanisms of atrial arrhythmogenesis in patients with paroxysmal atrial fibrillation. Circulation 129:145–156. https://doi.org/10.1161/CIRCULATIONAHA.113.006641

    Article  CAS  PubMed  Google Scholar 

  52. Westermeier R (2006) Sensitive, quantitative, and fast modifications for Coomassie blue staining of polyacrylamide gels. Proteomics 6(Suppl 2):61–64. https://doi.org/10.1002/pmic.200690121

    Article  PubMed  Google Scholar 

  53. Yan J, Kong W, Zhang Q, Beyer EC, Walcott G, Fast VG, Ai X (2013) c-Jun N-terminal kinase activation contributes to reduced connexin43 and development of atrial arrhythmias. Cardiovasc Res 97:589–597. https://doi.org/10.1093/cvr/cvs366

    Article  CAS  PubMed  Google Scholar 

  54. Yan J, Thomson JK, Wu X, Zhao W, Pollard AE, Ai X (2014) Novel methods of automated quantification of gap junction distribution and interstitial collagen quantity from animal and human atrial tissue sections. PLoS One 9:e104357. https://doi.org/10.1371/journal.pone.0104357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Yan J, Thomson JK, Zhao W, Wu X, Gao X, DeMarco D, Kong W, Tong M, Sun J, Bakhos M, Fast VG, Liang Q, Prabhu SD, Ai X (2017) The stress kinase JNK regulates gap junction Cx43 gene expression and promotes atrial fibrillation in the aged heart. J Mol Cell Cardiol 114:105–115. https://doi.org/10.1016/j.yjmcc.2017.11.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Yan J, Zhao W, Thomson JK, Gao X, DeMarco DM, Carrillo E, Chen B, Wu X, Ginsburg KS, Bakhos M, Bers DM, Anderson ME, Song LS, Fill M, Ai X (2018) Stress signaling JNK2 crosstalk with CaMKII underlies enhanced atrial arrhythmogenesis. Circ Res 122:821–835. https://doi.org/10.1161/CIRCRESAHA.117.312536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yao L, Chen X, Tian Y, Lu H, Zhang P, Shi Q, Zhang J, Liu Y (2012) Selection of housekeeping genes for normalization of RT-PCR in hypoxic neural stem cells of rat in vitro. Mol Biol Rep 39:569–576. https://doi.org/10.1007/s11033-011-0772-8

    Article  CAS  PubMed  Google Scholar 

  58. Zala D, Hinckelmann MV, Yu H, Lyra da Cunha MM, Liot G, Cordelieres FP, Marco S, Saudou F (2013) Vesicular glycolysis provides on-board energy for fast axonal transport. Cell 152:479–491. https://doi.org/10.1016/j.cell.2012.12.029

    Article  CAS  PubMed  Google Scholar 

  59. Zhong H, Simons JW (1999) Direct comparison of GAPDH, beta-actin, cyclophilin, and 28S rRNA as internal standards for quantifying RNA levels under hypoxia. Biochem Biophys Res Commun 259:523–526. https://doi.org/10.1006/bbrc.1999.0815

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National Institutes of Health [R01-HL113640 to XA].

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Rush University Medical Center, 1750 West Harrison St. 1255 Jelke South, Chicago, IL, 60612, USA

    Mei Yang, Jiajie Yan, Aimee Wu, Weiwei Zhao, Jin Qin, Xin Wu & Xun Ai

  2. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Steven M Pogwizd

  3. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, 210009, China

    Shengtao Yuan

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  1. Mei Yang
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This article is part of the special issue on Calcium Signal Dynamics in Cardiac Myocytes and Fibroblasts: Mechanisms in Pflügers Archiv—European Journal of Physiology

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Yang, M., Yan, J., Wu, A. et al. Alterations of housekeeping proteins in human aged and diseased hearts. Pflugers Arch - Eur J Physiol 473, 351–362 (2021). https://doi.org/10.1007/s00424-021-02538-x

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