Skip to main content
SpringerLink
Log in

Mitochondrial bioenergetics links inflammation and cardiac contractility in endotoxemia

  • Original Contribution
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

There is current awareness about the central role of mitochondrial dysfunction in the development of cardiac dysfunction in systemic inflammatory syndromes, especially in sepsis and endotoxemia. The aim of this work was to elucidate the mechanism that governs the link between the severity of the systemic inflammatory insult and mitochondrial function, analysing the consequences on heart function, particularly in cardiac contractile state. Female Sprague–Dawley rats were subjected to low-grade endotoxemia (i.p. injection LPS 0.5 mg kg−1 body weight) and severe endotoxemia (i.p. injection LPS 8 mg kg−1 body weight) for 6 h. Blood NO, as well as cardiac TNF-α and IL-1β mRNA, were found increased as the severity of the endotoxemia increases. Cardiac relaxation was altered only in severe endotoxemia, although contractile and lusitropic reserves were found impaired in both treatments in response to work-overload. Cardiac ultrastructure showed disorientation of myofibrillar structure in both endotoxemia degrees, but mitochondrial swelling and cristae disruption were only observed in severe endotoxemia. Mitochondrial ATP production, O2 consumption and mitochondrial inner membrane potential decreases were related to blood NO levels and mitochondrial protein nitration, leading to diminished ATP availability and impairment of contractile state. Co-treatment with the NOS inhibitor l-NAME or the administration of the NO scavenger c-PTIO leads to the observation that mitochondrial bioenergetics status depends on the degree of the inflammatory insult mainly determined by blood NO levels. Unravelling the mechanisms involved in the onset of sepsis and endotoxemia improves the interpretation of the pathology, and provides new horizons for novel therapeutic targets.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

ATP:

Adenosine triphosphate

ADP:

Adenosine diphosphate

BSA:

Bovine serum albumin

c-PTIO:

2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt

DAF:

4,5-Diaminofluorescein

DCF:

2′,7′-Dichlorofluorescein

ISO:

Isoproterenol

l-NAME:

Nω-nitro-l-arginine methyl ester hydrochloride

LPS:

Lipopolysaccharide

MM:

Mitochondrial membranes

NADH:

Nicotinamide adenine dinucleotide

NO:

Nitric oxide

NO −x :

Nitrite/nitrate

ONOO− :

Peroxynitrite

PMN:

Polymorphonuclear leukocytes

RCR:

Respiratory control ratio

ROS:

Reactive oxygen species

TNF-α:

Tumor necrosis factor

References

  1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC, Der Poll T, Vincent JL, Angus DC (2016) The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315:801–810. https://doi.org/10.1001/jama.2016.0287

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Cohen J, Vincent J-L, Adhikari NKJ, Machado FR, Angus DC, Calandra T, Jaton K, Giulieri S, Delaloye J, Opal S, Tracey K, van der Poll T, Pelfrene E (2015) Sepsis: a roadmap for future research. Lancet Infect Dis 15:581–614. https://doi.org/10.1016/S1473-3099(15)70112-X

    PubMed  Google Scholar 

  3. Thimmulappa RK, Scollick C, Traore K, Yates M, Trush MA, Liby KT, Sporn MB, Yamamoto M, Kensler TW, Biswal S (2006) Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun 351:883–889. https://doi.org/10.1016/j.bbrc.2006.10.102

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Morris MC, Gilliam EA, Li L (2014) Innate immune programing by endotoxin and its pathological consequences. Front Immunol 5:680. https://doi.org/10.3389/fimmu.2014.00680

    PubMed  Google Scholar 

  5. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti J-FF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772. https://doi.org/10.2337/db06-1491

    CAS  PubMed  Google Scholar 

  6. Frisard MI, McMillan RP, Marchand J, Wahlberg KA, Wu Y, Voelker KA, Heilbronn L, Haynie K, Muoio B, Li L, Hulver MW (2010) Toll-like receptor 4 modulates skeletal muscle substrate metabolism. Am J Physiol Endocrinol Metab 298:E988–E998. https://doi.org/10.1152/ajpendo.00307.2009

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Glaros TG, Chang S, Gilliam EA, Maitra U, Deng H, Li L (2013) Causes and consequences of low grade endotoxemia and inflammatory diseases. Front Biosci (Schol Ed) 5:754–765. https://doi.org/10.2741/s405

    Google Scholar 

  8. de Punder K, Pruimboom L (2015) Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability. Front Immunol 6:223. https://doi.org/10.3389/fimmu.2015.00223

    PubMed  PubMed Central  Google Scholar 

  9. Antonucci E, Fiaccadori E, Donadello K, Taccone FS, Franchi F, Scolletta S (2014) Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment. J Crit Care 29:500–511. https://doi.org/10.1016/j.jcrc.2014.03.028

    PubMed  Google Scholar 

  10. Celes MR, Prado CM, Rossi MA (2013) Sepsis: going to the heart of the matter. Pathobiology 80:70–86. https://doi.org/10.1159/000341640

    PubMed  Google Scholar 

  11. Fernandes CJ Jr, de Assuncao MS (2012) Myocardial dysfunction in sepsis: a large, unsolved puzzle. Crit Care Res Pr 2012:896430. https://doi.org/10.1155/2012/896430

    Google Scholar 

  12. Kakihana Y, Ito T, Nakahara M, Yamaguchi K, Yasuda T (2016) Sepsis-induced myocardial dysfunction: pathophysiology and management. J Intensive Care 4:22. https://doi.org/10.1186/s40560-016-0148-1

    PubMed  PubMed Central  Google Scholar 

  13. Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M (2002) Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360:219–223. https://doi.org/10.1016/S0140-6736(02)09459-X

    CAS  PubMed  Google Scholar 

  14. Carre JE, Orban JC, Re L, Felsmann K, Iffert W, Bauer M, Suliman HB, Piantadosi CA, Mayhew TM, Breen P, Stotz M, Singer M (2010) Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Respir Crit Care Med 182:745–751. https://doi.org/10.1164/rccm.201003-0326OC

    PubMed  PubMed Central  Google Scholar 

  15. Fink MP (2001) Cytopathic hypoxia. Mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis. Crit Care Clin 17:219–237. https://doi.org/10.1016/S0749-0704(05)70161-5

    CAS  PubMed  Google Scholar 

  16. Flierl M, Rittirsch D, Huber-Lang MS, Sarma JV, Ward PA (2008) Molecular events in the cardiomyopathy of sepsis. Mol Med 14:1. https://doi.org/10.2119/2007-00130.Flierl

    Google Scholar 

  17. Radi R, Cassina A, Hodara R, Quijano C, Castro L (2002) Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33:1451–1464. https://doi.org/10.1016/S0891-5849(02)01111-5

    CAS  PubMed  Google Scholar 

  18. Vanasco V, Saez T, Magnani ND, Pereyra L, Marchini T, Corach A, Vaccaro MI, Corach D, Evelson P, Alvarez S (2014) Cardiac mitochondrial biogenesis in endotoxemia is not accompanied by mitochondrial function recovery. Free Radic Biol Med 77:1–9. https://doi.org/10.1016/j.freeradbiomed.2014.08.009

    CAS  PubMed  Google Scholar 

  19. Bøtker HE, Hausenloy D, Andreadou I, Antonucci S, Boengler K, Davidson SM, Deshwal S, Devaux Y, Di Lisa F, Di Sante M, Efentakis P, Femminò S, García-Dorado D, Giricz Z, Ibanez B, Iliodromitis E, Kaludercic N, Kleinbongard P, Neuhäuser M, Ovize M, Pagliaro P, Rahbek-Schmidt M, Ruiz-Meana M, Schlüter K-D, Schulz R, Skyschally A, Wilder C, Yellon DM, Ferdinandy P, Heusch G (2018) Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. Basic Res Cardiol 113:39. https://doi.org/10.1007/s00395-018-0696-8

    PubMed  PubMed Central  Google Scholar 

  20. Alvarez S, Vico T, Vanasco V (2016) Cardiac dysfunction, mitochondrial architecture, energy production, and inflammatory pathways: interrelated aspects in endotoxemia and sepsis. Int J Biochem Cell Biol 81:307–314. https://doi.org/10.1016/j.biocel.2016.07.032

    CAS  PubMed  Google Scholar 

  21. Yao Y, Hu X, Feng X, Zhao Y, Song M, Wang C, Fan H (2019) Dexmedetomidine alleviates lipopolysaccharide-induced acute kidney injury by inhibiting the NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway. J Cell Biochem. https://doi.org/10.1002/jcb.29173

  22. Natanson C, Eichenholz PW, Danner RL, Eichacker PQ, Hoffman WD, Kuo GC, Banks SM, MacVittie TJ, Parrillo JE (1989) Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med 169:823–832. https://doi.org/10.1084/jem.169.3.823

    CAS  PubMed  Google Scholar 

  23. Zhang H-X, Liu S-J, Tang X-L, Duan G-L, Ni X, Zhu X-Y, Liu Y-J, Wang C-N (2016) H2S attenuates LPS-induced acute lung injury by reducing oxidative/nitrative stress and inflammation. Cell Physiol Biochem 40:1603–1612. https://doi.org/10.1159/000453210

    CAS  PubMed  Google Scholar 

  24. Miura K, Yamanaka S, Ebara T, Okumura M, Imanishi M, Kim S, Nakatani T, Iwao H (2000) Effects of nitric oxide scavenger, carboxy-PTIO on endotoxin-induced alterations in systemic hemodynamics in rats. Jpn J Pharmacol 82:261–264

    CAS  PubMed  Google Scholar 

  25. Yoshida M, Akaike T, Wada Y, Sato K, Ikeda K, Ueda S, Maeda H (1994) Therapeutic effects of imidazolineoxyl N-oxide against endotoxin shock through its direct nitric oxide-scavenging activity. Biochem Biophys Res Commun 202:923–930. https://doi.org/10.1006/bbrc.1994.2018

    CAS  PubMed  Google Scholar 

  26. Marchini T, Magnani ND, Paz ML, Vanasco V, Tasat D, Gonzalez Maglio DH, Alvarez S, Evelson PA (2014) Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to residual oil fly ash. Toxicol Appl Pharmacol 274:274–282. https://doi.org/10.1016/j.taap.2013.11.013

    CAS  PubMed  Google Scholar 

  27. Walrand S, Valeix S, Rodriguez C, Ligot P, Chassagne J, Vasson M-P (2003) Flow cytometry study of polymorphonuclear neutrophil oxidative burst: a comparison of three fluorescent probes. Clin Chim Acta 331:103–110. https://doi.org/10.1016/S0009-8981(03)00086-X

    CAS  PubMed  Google Scholar 

  28. Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71. https://doi.org/10.1006/niox.2000.0319

    CAS  PubMed  Google Scholar 

  29. Buchholz B, D’Annunzio VV, Giani JF, Siachoque N, Dominici FP, Turyn D, Perez V, Donato MM, Gelpi RJ (2014) Ischemic postconditioning reduces infarct size through the alpha1-adrenergic receptor pathway. J Cardiovasc Pharmacol 63:504–511. https://doi.org/10.1097/fjc.0000000000000074

    CAS  PubMed  Google Scholar 

  30. Sutherland FJ, Shattock MJ, Baker KE, Hearse DJ (2003) Mouse isolated perfused heart: characteristics and cautions. Clin Exp Pharmacol Physiol 30:867–878. https://doi.org/10.1046/j.1440-1681.2003.03925.x

    CAS  PubMed  Google Scholar 

  31. Jain M, Lim CC, Nagata K, Davis VM, Milstone DS, Liao R, Mortensen RM (2001) Targeted inactivation of Galpha(i) does not alter cardiac function or beta-adrenergic sensitivity. Am J Physiol Hear Circ Physiol 280:H569–H575. https://doi.org/10.1152/ajpheart.2001.280.2.H569

    CAS  Google Scholar 

  32. Marchini T, D’Annunzio V, Paz ML, Cáceres L, Garcés M, Perez V, Tasat D, Vanasco V, Magnani N, Gonzalez Maglio D, Gelpi RJ, Alvarez S, Evelson P (2015) Selective TNF-α targeting with infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter. Am J Physiol Heart Circ Physiol 309:H1621–H1628. https://doi.org/10.1152/ajpheart.00359.2015

    CAS  PubMed  Google Scholar 

  33. Mela L, Seitz S (1979) Isolation of mitochondria with emphasis on heart mitochondria from small amounts of tissue. Methods Enzym 55:39–46

    CAS  Google Scholar 

  34. Cadenas E, Boveris A (1980) Enhancement of hydrogen peroxide formation by protophores and ionophores in antimycin-supplemented mitochondria. Biochem J 188:31–37

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275. https://doi.org/10.1016/0304-3894(92)87011-4

    CAS  PubMed  Google Scholar 

  36. Boveris A, Costa LE, Cadenas E, Poderoso JJ (1999) Regulation of mitochondrial respiration by adenosine diphosphate, oxygen, and nitric oxide. Methods Enzym 301:188–198

    CAS  Google Scholar 

  37. Vives-Bauza C, Yang L, Manfredi G (2007) Assay of mitochondrial ATP synthesis in animal cells and tissues. Methods Cell Biol 80:155–171. https://doi.org/10.1016/S0091-679X(06)80007-5

    CAS  PubMed  Google Scholar 

  38. Marchini T, Magnani N, D’Annunzio V, Tasat D, Gelpi RJ, Alvarez S, Evelson P (2013) Impaired cardiac mitochondrial function and contractile reserve following an acute exposure to environmental particulate matter. Biochim Biophys Acta Gen Subj 1830:2545–2552. https://doi.org/10.1016/j.bbagen.2012.11.012

    CAS  Google Scholar 

  39. Haines TH, Dencher NA (2002) Cardiolipin: a proton trap for oxidative phosphorylation. FEBS Lett 528:35–39. https://doi.org/10.1016/S0014-5793(02)03292-1

    CAS  PubMed  Google Scholar 

  40. Vanasco V, Magnani ND, Cimolai MC, Valdez LB, Evelson P, Boveris A, Alvarez S (2012) Endotoxemia impairs heart mitochondrial function by decreasing electron transfer, ATP synthesis and ATP content without affecting membrane potential. J Bioenerg Biomembr 44:243–252. https://doi.org/10.1007/s10863-012-9426-3

    CAS  PubMed  Google Scholar 

  41. Yonetani T (1967) Cytochrome oxidase: beef heart. In: Methods in enzymology. pp 332–335. https://doi.org/10.1016/0076-6879(67)10062-1

    Google Scholar 

  42. Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ (2003) Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 278:36027–36031. https://doi.org/10.1074/jbc.m304854200

    CAS  PubMed  Google Scholar 

  43. Bryan NS, Grisham MB (2007) Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med 43:645–657. https://doi.org/10.1016/j.freeradbiomed.2007.04.026

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Antunes F, Cadenas E (2001) Cellular titration of apoptosis with steady state concentrations of H2O2: submicromolar levels of H2O2 induce apoptosis through fenton chemistry independent of the cellular thiol state. Free Radic Biol Med 30:1008–1018. https://doi.org/10.1016/S0891-5849(01)00493-2

    CAS  PubMed  Google Scholar 

  45. Vanasco V, Evelson P, Boveris A, Alvarez S (2010) In situ and real time muscle chemiluminescence determines singlet oxygen involvement in oxidative damage during endotoxemia. Chem Biol Interact 184:313–318. https://doi.org/10.1016/j.cbi.2010.01.011

    CAS  PubMed  Google Scholar 

  46. Connelly L, Palacios-Callender M, Ameixa C, Moncada S, Hobbs AJ (2001) Biphasic regulation of NF-kappa B activity underlies the pro- and anti-inflammatory actions of nitric oxide. J Immunol 166:3873–3881. https://doi.org/10.4049/jimmunol.166.6.3873

    CAS  PubMed  Google Scholar 

  47. Walley KR, McDonald TE, Higashimoto Y, Hayashi S (1999) Modulation of proinflammatory cytokines by nitric oxide in murine acute lung injury. Am J Respir Crit Care Med 160:698–704. https://doi.org/10.1164/ajrccm.160.2.9809081

    CAS  PubMed  Google Scholar 

  48. Millar CGM, Thiemermann C (2002) Carboxy-PTIO, a scavenger of nitric oxide, selectively inhibits the increase in medullary perfusion and improves renal function in endotoxemia. Shock 18:64–68

    PubMed  Google Scholar 

  49. van de Sandt AM, Windler R, Gödecke A, Ohlig J, Zander S, Reinartz M, Graf J, van Faassen EE, Rassaf T, Schrader J, Kelm M, Merx MW (2013) Endothelial NOS (NOS3) impairs myocardial function in developing sepsis. Basic Res Cardiol 108:330. https://doi.org/10.1007/s00395-013-0330-8

    PubMed  PubMed Central  Google Scholar 

  50. Ortiz F, García JA, Acuña-Castroviejo D, Doerrier C, López A, Venegas C, Volt H, Luna-Sánchez M, López LC, Escames G (2014) The beneficial effects of melatonin against heart mitochondrial impairment during sepsis: inhibition of iNOS and preservation of nNOS. J Pineal Res 56:71–81. https://doi.org/10.1111/jpi.12099

    CAS  PubMed  Google Scholar 

  51. Jarkovska D, Markova M, Horak J, Nalos L, Benes J, Al-Obeidallah M, Tuma Z, Sviglerova J, Kuncova J, Matejovic M, Stengl M (2018) Cellular mechanisms of myocardial depression in porcine septic shock. Front Physiol 9:726. https://doi.org/10.3389/fphys.2018.00726

    PubMed  PubMed Central  Google Scholar 

  52. Kirkeboen KA, Strand OA (1999) The role of nitric oxide in sepsis—an overview. Acta Anaesthesiol Scand 43:275–288

    CAS  PubMed  Google Scholar 

  53. Aird WC (2003) The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 101:3765–3777. https://doi.org/10.1182/blood-2002-06-1887

    CAS  PubMed  Google Scholar 

  54. Predonzani A, Cali B, Agnellini AH, Molon B, Calì B, Agnellini AH, Molon B, Cali B, Agnellini AH, Molon B (2015) Spotlights on immunological effects of reactive nitrogen species: when inflammation says nitric oxide. World J Exp Med 5:64–76. https://doi.org/10.5493/wjem.v5.i2.64

    PubMed  PubMed Central  Google Scholar 

  55. Cortese-Krott MM, Rodriguez-Mateos A, Sansone R, Kuhnle GGC, Thasian-Sivarajah S, Krenz T, Horn P, Krisp C, Wolters D, Heiß C, Kröncke K-D, Hogg N, Feelisch M, Kelm M (2012) Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease. Blood 120:4229–4237. https://doi.org/10.1182/blood-2012-07-442277

    CAS  PubMed  Google Scholar 

  56. Kleinbongard P, Schulz R, Rassaf T, Lauer T, Dejam A, Jax T, Kumara I, Gharini P, Kabanova S, Ozüyaman B, Schnürch H-G, Gödecke A, Weber A-A, Robenek M, Robenek H, Bloch W, Rösen P, Kelm M (2006) Red blood cells express a functional endothelial nitric oxide synthase. Blood 107:2943–2951. https://doi.org/10.1182/blood-2005-10-3992

    CAS  PubMed  Google Scholar 

  57. Merx MW, Gorressen S, van de Sandt AM, Cortese-Krott MM, Ohlig J, Stern M, Rassaf T, Gödecke A, Gladwin MT, Kelm M (2014) Depletion of circulating blood NOS3 increases severity of myocardial infarction and left ventricular dysfunction. Basic Res Cardiol 109:398. https://doi.org/10.1007/s00395-013-0398-1

    PubMed  Google Scholar 

  58. Liao R, Podesser BK, Lim CC (2012) The continuing evolution of the Langendorff and ejecting murine heart: new advances in cardiac phenotyping. Am J Physiol Heart Circ Physiol 303:H156–H167. https://doi.org/10.1152/ajpheart.00333.2012

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Bell RM, Mocanu MM, Yellon DM (2011) Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol 50:940–950. https://doi.org/10.1016/j.yjmcc.2011.02.018

    CAS  PubMed  Google Scholar 

  60. Paula TD, Silva BR, Grando MD, Souza HCD, Bendhack LM (2018) Activation of TP receptors induces high release of PGI2 in coronary arteries of renal hypertensive rats. J Mol Cell Cardiol 122:125–133. https://doi.org/10.1016/j.yjmcc.2018.08.007

    CAS  PubMed  Google Scholar 

  61. Kane GC, Karon BL, Mahoney DW, Redfield MM, Roger VL, Burnett JC, Jacobsen SJ, Rodeheffer RJ (2011) Progression of left ventricular diastolic dysfunction and risk of heart failure. JAMA 306:856–863. https://doi.org/10.1001/jama.2011.1201

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Avlas O, Fallach R, Shainberg A, Porat E, Hochhauser E (2011) Toll-like receptor 4 stimulation initiates an inflammatory response that decreases cardiomyocyte contractility. Antioxid Redox Signal 15:1895–1909. https://doi.org/10.1089/ars.2010.3728

    CAS  PubMed  Google Scholar 

  63. Hill BGG, Dranka BPP, Zou L, Chatham JCC, Darley-Usmar VMM (2009) Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal. Biochem J 424:99–107. https://doi.org/10.1042/BJ20090934

    CAS  PubMed  Google Scholar 

  64. Cimolai MC, Vanasco V, Marchini T, Magnani ND, Evelson P, Alvarez S (2014) Alpha-lipoic acid protects kidney from oxidative stress and mitochondrial dysfunction associated to inflammatory conditions. Food Funct 5:3143–3150. https://doi.org/10.1039/c4fo00489b

    CAS  PubMed  Google Scholar 

  65. Boveris A, Carreras MC, Poderoso JJ (2010) The regulation of cell energetics and mitochondrial signaling by nitric oxide. In: Louise JI (ed) Nitric oxide biology and pathobiology, 2nd edn. pp 441–482. https://doi.org/10.1016/B978-0-12-373866-0.00013-7

    Google Scholar 

  66. Valdez LB, Bombicino SS, Iglesias DE, Rukavina Mikusic I, Boveris A (2018) Mitochondrial peroxynitrite generation is mainly driven by superoxide steady-state concentration rather than by nitric oxide steady-state concentration. Int J Mol Biol Open Access 3:56–61. https://doi.org/10.15406/ijmboa.2018.03.00051

    Google Scholar 

Download references

Acknowledgements

The authors are grateful to Daniel Gonzalez Maglio for the helpful assistance with ELISA assays, to Elizabeth Robello for the assistance with EPR assays, and to Pablo La Padula for his helpful analysis of cardiac function.

Funding

This work was supported by research Grants from the Secretaría de Ciencia y Técnica, University of Buenos Aires [UBACYT2016 20020150100186BA]; Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT) [PICT 2013-3227]; and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) [PIP 11220120100321].

Author information

Authors and Affiliations

  1. Instituto de Bioquímica y Medicina Molecular (IBIMOL), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina

    Tamara Antonela Vico, Timoteo Marchini, Valeria Calabró, Mariana Garcés, Tamara Mazo, Verónica D’Annunzio, Ricardo J. Gelpi, Pablo Evelson, Virginia Vanasco & Silvia Alvarez

  2. Departamento de Química Analítica y Fisicoquímica, Facultad de Farmacia y Bioquímica, Cátedra de Fisicoquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina

    Tamara Antonela Vico, Juan Santiago Adán Areán, Virginia Vanasco & Silvia Alvarez

  3. Departamento de Química Analítica y Fisicoquímica, Facultad de Farmacia y Bioquímica, Cátedra de Química General e Inorgánica, Universidad de Buenos Aires, Buenos Aires, Argentina

    Timoteo Marchini, Mariana Garcés & Pablo Evelson

  4. Servicio de Huellas Digitales Genéticas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

    Santiago Ginart & Daniel Corach

  5. División Patología, Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), CONICET-GCBA, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

    Mario Alejandro Lorenzetti

  6. Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina

    Mariana Cristina Ferrero

  7. Departamento de Patología, Instituto de Fisiopatología Cardiovascular, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    Tamara Mazo, Verónica D’Annunzio & Ricardo J. Gelpi

Authors
  1. Tamara Antonela Vico
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timoteo Marchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Santiago Ginart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mario Alejandro Lorenzetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juan Santiago Adán Areán
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Valeria Calabró
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mariana Garcés
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mariana Cristina Ferrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tamara Mazo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Verónica D’Annunzio
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ricardo J. Gelpi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Daniel Corach
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Pablo Evelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Virginia Vanasco
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Silvia Alvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Virginia Vanasco or Silvia Alvarez.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 54 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vico, T.A., Marchini, T., Ginart, S. et al. Mitochondrial bioenergetics links inflammation and cardiac contractility in endotoxemia. Basic Res Cardiol 114, 38 (2019). https://doi.org/10.1007/s00395-019-0745-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00395-019-0745-y

Keywords

Search

Navigation