Abstract
Cardiolipin (CL) is a class of phospholipid tightly associated with the mitochondria functions and a prime target of oxidative stress. Peroxidation of CL dissociates its bound cytochrome C, a phenomenon that reflects oxidative stress sustained by the organ and a trigger for the intrinsic apoptotic pathway. However, CL distribution in normal organ tissues has yet to be documented. Fresh rat organs were snap-frozen, cut into cryosections that were subsequently desalted with ammonium acetate solution, and vacuum-dried. CL distribution in situ was determined using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technique on sections sublimed with 2,5-dihydroxybenzoic acid. CL images in rat cardiac ventricular section showed a homogeneous distribution of a single m/z 1447.9 ion species that was confirmed as the (18:2)4 CL by tandem mass spectrometry. The presence of low abundant (18:2)3(18:1) CL with the bulk (18:2)4 CL in quadriceps femoris rendered the muscle CL exhibiting a slightly deviated isotopic pattern from that of cardiac muscle. In rat liver, MALDI-MSI unveiled three CL-containing mass ranges, each with a unique in situ distribution pattern. Co-registration of the CL ion images with its stained liver section image further revealed the association of CLs in each mass range with the functional zones in the liver parenchyma and suggests the participation of in situ CLs with localized hepatic functions such as oxidation, conjugation, and detoxification. The advances in CL imaging offer an approach with molecular accuracy to reveal potentially dysregulated metabolic machineries in acute and chronic diseased states.
Similar content being viewed by others
References
Pfeiffer K, Gohil V, Stuart RA, Hunte C, Brandt U, Greenberg ML, Schagger H (2003) Cardiolipin stabilizes respiratory chain supercomplexes. J Biol Chem 278(52):52873–52880
Ott M, Zhivotovsky B, Orrenius S (2007) Role of cardiolipin in cytochrome c release from mitochondria. Cell Death Differ 14(7):1243–1247
Paradies G, Petrosillo G, Paradies V, Ruggiero FM (2009) Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease. Cell Calcium 45(6):643–650
Stevens A, Lowe JS (2005) Human histology. 3rd edn. Philadelphia, PN, Elsevier
Hijmans BS, Grefhorst A, Oosterveer MH, Groen AK (2013) Zonation of glucose and fatty acid metabolism in the liver: mechanism and metabolic consequences. Biochimie. doi:10.1016/j.biochi.2013.06.007
Chicco AJ, Sparagna GC (2007) Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol 292(1):C33–C44
Bayir H, Tyurin VA, Tyurina YY, Viner R, Ritov V, Amoscato AA, Zhao Q, Zhang XJ, Janesko-Feldman KL, Alexander H, Basova LV, Clark RS, Kochanek PM, Kagan VE (2007) Selective early cardiolipin peroxidation after traumatic brain injury: an oxidative lipidomics analysis. Ann Neurol 62(2):154–169
Hsu FF, Turk J (2006) Characterization of cardiolipin as the sodiated ions by positive-ion electrospray ionization with multiple stage quadrupole ion-trap mass spectrometry. J Am Soc Mass Spectrom 17(8):1146–1157
Hsu FF, Turk J (2006) Characterization of cardiolipin from Escherichia coli by electrospray ionization with multiple stage quadrupole ion-trap mass spectrometric analysis of [M − 2H + Na]− ions. J Am Soc Mass Spectrom 17(3):420–429
Hsu FF, Turk J, Rhoades ER, Russell DG, Shi Y, Groisman EA (2005) Structural characterization of cardiolipin by tandem quadrupole and multiple-stage quadrupole ion-trap mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom 16(4):491–504
Tyurina YY, Tyurin VA, Kaynar AM, Kapralova VI, Wasserloos K, Li J, Mosher M, Wright L, Wipf P, Watkins S, Pitt BR, Kagan VE (2010) Oxidative lipidomics of hyperoxic acute lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation. Am J Physiol Lung Cell Mol Physiol 299(1):L73–L85
Maciel E, Domingues P, Domingues MR (2011) Liquid chromatography/tandem mass spectrometry analysis of long-chain oxidation products of cardiolipin induced by the hydroxyl radical. Rapid Commun Mass Spectrom 25(2):316–326
Kim J, Hoppel CL (2013) Comprehensive approach to the quantitative analysis of mitochondrial phospholipids by HPLC-MS. J Chromatogr B Anal Technol Biomed Life Sci 912:105–114
Dannenberger D, Suss R, Teuber K, Fuchs B, Nuernberg K, Schiller J (2010) The intact muscle lipid composition of bulls: an investigation by MALDI-TOF MS and 31P NMR. Chem Phys Lipids 163(2):157–164
Stubiger G, Pittenauer E, Allmaier G (2008) MALDI seamless postsource decay fragment ion analysis of sodiated and lithiated phospholipids. Anal Chem 80(5):1664–1678
Wang HY, Jackson SN, Woods AS (2007) Direct MALDI-MS analysis of cardiolipin from rat organs sections. J Am Soc Mass Spectrom 18(3):567–577
Yurkova I, Huster D, Arnhold J (2009) Free radical fragmentation of cardiolipin by cytochrome c. Chem Phys Lipids 158(1):16–21
Yurkova IL, Arnhold J, Fitzl G, Huster D (2011) Fragmentation of mitochondrial cardiolipin by copper ions in the Atp7b−/− mouse model of Wilson's disease. Chem Phys Lipids 164(5):393–400
Eibisch M, Zellmer S, Gebhardt R, Suss R, Fuchs B, Schiller J (2011) Phosphatidylcholine dimers can be easily misinterpreted as cardiolipins in complex lipid mixtures: a matrix-assisted laser desorption/ionization time-of-flight mass spectrometric study of lipids from hepatocytes. Rapid Commun Mass Spectrom 25(18):2619–2626
Thomas A, Charbonneau JL, Fournaise E, Chaurand P (2012) Sublimation of new matrix candidates for high spatial resolution imaging mass spectrometry of lipids: enhanced information in both positive and negative polarities after 1,5-diaminonapthalene deposition. Anal Chem 84(4):2048–2054
Castellino S, Groseclose MR, Wagner D (2011) MALDI imaging mass spectrometry: bridging biology and chemistry in drug development. Bioanalysis 3(21):2427–2441
Hsieh Y, Chen J, Korfmacher WA (2007) Mapping pharmaceuticals in tissues using MALDI imaging mass spectrometry. J Pharmacol Toxicol Methods 55(2):193–200
Prideaux B, Stoeckli M (2012) Mass spectrometry imaging for drug distribution studies. J Proteome 75(16):4999–5013
Sugiura Y, Setou M (2010) Imaging mass spectrometry for visualization of drug and endogenous metabolite distribution: toward in situ pharmacometabolomes. J Neuroimmune Pharmacol 5(1):31–43
Fournier I, Wisztorski M, Salzet M (2008) Tissue imaging using MALDI-MS: a new frontier of histopathology proteomics. Expert Rev Proteomics 5(3):413–424
Franck J, Arafah K, Elayed M, Bonnel D, Vergara D, Jacquet A, Vinatier D, Wisztorski M, Day R, Fournier I, Salzet M (2009) MALDI imaging mass spectrometry: state of the art technology in clinical proteomics. Mol Cell Proteomics 8(9):2023–2033
Wisztorski M, Lemaire R, Stauber J, Menguelet SA, Croix D, Mathe OJ, Day R, Salzet M, Fournier I (2007) New developments in MALDI imaging for pathology proteomic studies. Curr Pharm Des 13(32):3317–3324
Wong SC, Chan CM, Ma BB, Lam MY, Choi GC, Au TC, Chan AS, Chan AT (2009) Advanced proteomic technologies for cancer biomarker discovery. Expert Rev Proteomics 6(2):123–134
Fernandez JA, Ochoa B, Fresnedo O, Giralt MT, Rodriguez-Puertas R (2011) Matrix-assisted laser desorption ionization imaging mass spectrometry in lipidomics. Anal Bioanal Chem 401(1):29–51
Goto-Inoue N, Hayasaka T, Zaima N, Setou M (2011) Imaging mass spectrometry for lipidomics. Biochim Biophys Acta 1811(11):961–969
Harkewicz R, Dennis EA (2011) Applications of mass spectrometry to lipids and membranes. Ann Rev Biochem 80:301–325
Sparvero LJ, Amoscato AA, Kochanek PM, Pitt BR, Kagan VE, Bayir H (2010) Mass-spectrometry based oxidative lipidomics and lipid imaging: applications in traumatic brain injury. J Neurochem 115(6):1322–1336
Wang HY, Wu HW, Tsai PJ, Liu CB (2012) MALDI-mass spectrometry imaging of desalted rat brain sections reveals ischemia-mediated changes of lipids. Anal Bioanal Chem 404(1):113–124
Wang HY, Liu CB, Wu HW (2011) A simple desalting method for direct MALDI mass spectrometry profiling of tissue lipids. J Lipid Res 52(4):840–849
Strohalm M, Hassman M, Kosata B, Kodicek M (2008) mMass data miner: an open source alternative for mass spectrometric data analysis. Rapid Commun Mass Spectrom 22(6):905–908
Strohalm M, Kavan D, Novak P, Volny M, Havlicek V (2010) mMass 3: a cross-platform software environment for precise analysis of mass spectrometric data. Anal Chem 82(11):4648–4651
Hankin JA, Barkley RM, Murphy RC (2007) Sublimation as a method of matrix application for mass spectrometric imaging. J Am Soc Mass Spectrom 18(9):1646–1652
Murphy RC, Hankin JA, Barkley RM (2009) Imaging of lipid species by MALDI mass spectrometry. J Lipid Res 50(Suppl):S317–S322
Murphy RC, Hankin JA, Barkley RM, Zemski Berry KA (2011) MALDI imaging of lipids after matrix sublimation/deposition. Biochim Biophys Acta 1811(11):970–975
Lapthorn C, Pullen F, Chowdhry BZ (2013) Ion mobility spectrometry-mass spectrometry (IMS-MS) of small molecules: separating and assigning structures to ions. Mass Spectrom Rev 32(1):43–71
Benard S, Arnhold J, Lehnert M, Schiller J, Arnold K (1999) Experiments towards quantification of saturated and polyunsaturated diacylglycerols by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. Chem Phys Lipids 100:115–125
Schaper J, Meiser E, Stammler G (1985) Ultrastructural morphometric analysis of myocardium from dogs, rats, hamsters, mice, and from human hearts. Circ Res 56(3):377–391
Berger A, German JB, Gershwin ME (1993) Biochemistry of cardiolipin: sensitivity to dietary fatty acids. Adv Food Nutr Res 37:259–338
Ross MH, Kaye GI, Pawlina W (2003) Histology: a text and atlas. Williams & WIlkins, Baltimore
Jungermann K, Thurman RG (1992) Hepatocyte heterogeneity in the metabolism of carbohydrates. Enzyme 46(1–3):33–58
Haussinger D, Lamers WH, Moorman AF (1992) Hepatocyte heterogeneity in the metabolism of amino acids and ammonia. Enzyme 46(1–3):72–93
Bass NM (1990) Fatty acid-binding protein expression in the liver: its regulation and relationship to the zonation of fatty acid metabolism. Mol Cell Biochem 98(1–2):167–176
Jungermann K, Kietzmann T (2000) Oxygen: modulator of metabolic zonation and disease of the liver. Hepatology 31(2):255–260
Jungermann K, Katz N (1982) Functional hepatocellular heterogeneity. Hepatology 2(3):385–395
Miyamura N, Nakamura T, Goto-Inoue N, Zaima N, Hayasaka T, Yamasaki T, Terai S, Sakaida I, Setou M, Nishina H (2011) Imaging mass spectrometry reveals characteristic changes in triglyceride and phospholipid species in regenerating mouse liver. Biochem Biophys Res Commun 408(1):120–125
Wattacheril J, Seeley EH, Angel P, Chen H, Bowen BP, Lanciault C, Caprioli RM, Abumrad N, Flynn CR (2013) Differential intrahepatic phospholipid zonation in simple steatosis and nonalcoholic steatohepatitis. PLoS One 8(2):e57165
Acknowledgments
This study was sponsored by National Scientific Council, Taiwan (grant No: NSC-99-2320-B-110-001-MY3), by Veterans General Hospital-Kaohsiung-National Sun Yat-Sen University Joint Research Consortium (grant No: VGHNSU101-002 and VGHNSU 102–004), and by "Aim for the Top University Plan" of National Sun Yat-Sen University, Taiwan. The authors acknowledge the generous support of Dr. Jentaie Shiea, Department of Chemistry, National Sun Yat-Sen University, Taiwan, for the use of MALDI-TOF/TOF instrument.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(PDF 1849 kb)
Rights and permissions
About this article
Cite this article
Wang, HY.J., Wu, HW., Tsai, PJ. et al. Matrix-assisted laser desorption/ionization mass spectrometry imaging of cardiolipins in rat organ sections. Anal Bioanal Chem 406, 565–575 (2014). https://doi.org/10.1007/s00216-013-7492-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-013-7492-y