Polyamines pp 395-408 | Cite as

Use of Polyamine Metabolites as Markers for Stroke and Renal Failure

  • Kazuei Igarashi
  • Keiko Kashiwagi
Part of the Methods in Molecular Biology book series (MIMB, volume 720)


Acrolein and H2O2 are among the metabolic products of spermine and spermidine, and it was found that acrolein was more toxic than H2O2. It was determined whether acrolein can serve as a biochemical marker for stroke (brain infarction) and chronic renal failure. Since acrolein rapidly reacts with lysine residues in protein, protein-conjugated acrolein (PC-Acro) was measured. PC-Acro was increased at the locus of brain infarction and in plasma in a mouse model of stroke involving photochemically induced thrombosis. An increase in PC-Acro in plasma was found to be a good biochemical marker in patients with stroke or with chronic renal failure. Using a receiver operating characteristic curve, the combined measurement of PC-Acro, IL-6 and CRP together with age indicated silent brain infarction (SBI) with 89% sensitivity and 91% specificity. The procedures to measure PC-Acro and polyamine oxidases [spermine oxidase (SMO) and acetylpolyamine oxidase (ACPAD)], and its application as markers in stroke and chronic renal failure are described in this chapter.

Key words

Acrolein Biochemical marker Brain infarction Chronic renal failure Polyamine metabolite Polyamine oxidase 



We are grateful to Drs. K. Williams and A. J. Michael for critical reading of the manuscript prior to submission. This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.


  1. 1.
    Igarashi K, Kashiwagi K (2000) Polyamines: mysterious modulators of cellular functions. Biochem Biophys Res Commun 271:559–564PubMedCrossRefGoogle Scholar
  2. 2.
    Igarashi K, Kashiwagi K (2010) Modulation of cellular function by polyamines. Int J Biochem Cell Biol 42:39–51PubMedCrossRefGoogle Scholar
  3. 3.
    Gaugas JM, Dewey DL (1979) Evidence for serum binding of oxidized spermine and its potent G1-phase inhibition of cell proliferation. Br J Cancer 39:548–557PubMedCrossRefGoogle Scholar
  4. 4.
    Bachrach U (1970) Oxidized polyamines. Ann N Y Acad Sci 171:939–956CrossRefGoogle Scholar
  5. 5.
    Tabor CW, Tabor H, Bachrach U (1964) Identification of the aminoaldehydes produced by theoxidation of spermine and spermidine with purified plasma amine oxidase. J Biol Chem 239:2194–2203PubMedGoogle Scholar
  6. 6.
    Sharmin S, Sakata K, Kashiwagi K, Ueda S, Iwasaki S, Shirahata A, Igarashi K (2001) Polyamine cytotoxicity in the presence of bovine serum amine oxidase. Biochem Biophys Res Commun 282:228–235PubMedCrossRefGoogle Scholar
  7. 7.
    Campbell RA, Talwalkar Y, Bartos D, Bartos F, Musgrave J, Harner M, Puri H, Grettie D, Dolney AM, Loggan B (1978) Polyamines, uremia and hemodialysis. In: Campbell RA, Morris DR, Bartos D, Daves GD Jr (eds) Advances in polyamine research. Raven, New York, pp 319–343Google Scholar
  8. 8.
    Sakata K, Kashiwagi K, Sharmin S, Ueda S, Irie Y, Murotani N, Igarashi K (2003) Increase in putrescine, amine oxidase, and acrolein in plasma of renal failure patients. Biochem Biophys Res Commun 305:143–149PubMedCrossRefGoogle Scholar
  9. 9.
    Igarashi K, Ueda S, Yoshida K, Kashiwagi K (2006) Polyamines in renal failure. Amino Acids 31:477–483PubMedCrossRefGoogle Scholar
  10. 10.
    Tomitori H, Usui T, Saeki N, Ueda S, Kase H, Nishimura K, Kashiwagi K, Igarashi K (2005) Polyamine oxidase and acrolein as novel biochemical markers for diagnosis of cerebral stroke. Stroke 36:2609–2613PubMedCrossRefGoogle Scholar
  11. 11.
    Yoshida M, Tomitori H, Machi Y, Katagiri D, Ueda S, Horiguchi K, Kobayashi E, Saeki N, Nishimura K, Ishii I, Kashiwagi K, Igarashi K (2009) Acrolein, IL-6 and CRP as markers of silent brain infarction. Atherosclerosis 203:557–562PubMedCrossRefGoogle Scholar
  12. 12.
    Ayusawa D, Iwata K, Seno T (1981) Alteration of ribonucleotide reductase in aphidicolin-resistant mutants of mouse FM3A cells with associated resistance to arabinosyladenine and arabinosylcytosine. Somatic Cell Genet 7:27–42PubMedCrossRefGoogle Scholar
  13. 13.
    Tanaka Y, Marumo T, Omura T, Yoshida S (2007) Quantitative assessments of cerebral ­vascular damage with a silicon rubber casting method in photochemically-induced thrombotic stroke rat models. Life Sci 81:1381–1388PubMedCrossRefGoogle Scholar
  14. 14.
    Saiki R, Nishimura K, Ishii I, Omura T, Okuyama S, Kashiwagi K, Igarashi K (2009) Intense correlation between brain infarction and protein-conjugated acrolein. Stroke 40:3356–3361PubMedCrossRefGoogle Scholar
  15. 15.
    Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (London) 227:680–685CrossRefGoogle Scholar
  16. 16.
    Nielsen PJ, Manchester KL, Towbin H, Gordon J, Thomas G (1982) The phosphorylation of ribosomal protein S6 in rat tissues following cycloheximide injection, in diabetes, and after denervation of diaphragm. A simple immunological determination of the extent of S6 phosphorylation on protein blots. J Biol Chem 257:12316–12321PubMedGoogle Scholar
  17. 17.
    Uchida K, Kanematsu M, Morimitsu Y, Osawa T, Noguchi N, Niki E (1998) Acrolein is a product of lipid peroxidation reaction. Formation of free acrolein and its conjugate with lysine residues in oxidized low density lipoproteins. J Biol Chem 273:16058–16066PubMedCrossRefGoogle Scholar
  18. 18.
    Igarashi K, Kashiwagi K, Hamasaki H, Miura A, Kakegawa T, Hirose S, Matsuzaki S (1986) Formation of a compensatory polyamine by Escherichia coli polyamine-requiring mutants during growth in the absence of polyamines. J Bacteriol 166:128–134PubMedGoogle Scholar
  19. 19.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  20. 20.
    Hoshi T, Kitagawa K, Yamagami H, Furukado S, Hougaku H, Hori M (2005) Relations of serum high-sensitivity C-reactive protein and interleukin-6 levels with silent brain infarction. Stroke 36:768–772PubMedCrossRefGoogle Scholar
  21. 21.
    Henry JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143:29–36Google Scholar
  22. 22.
    Ellenius J, Groth T, Lindahl B, Wallentin L (1997) Early assessment of patients with suspected acute myocardial infarction by biochemical monitoring and neural network analysis. Clin Chem 43:1919–1925PubMedGoogle Scholar
  23. 23.
    Brenner H, Gefeller O (1997) Variation of sensitivity, specificity, likelihood ratios and predictive values with disease prevalence. Stat Med 16:981–991PubMedCrossRefGoogle Scholar
  24. 24.
    Dogan A, Rao AM, Hatcher J, Rao VL, Baskaya MK, Dempsey RJ (1999) Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral artery occlusion. J Neurochem 72:765–770PubMedCrossRefGoogle Scholar
  25. 25.
    Kobayashi S, Okada K, Koide H, Bokura H, Yamaguchi S (1997) Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke 28:1932–1939PubMedCrossRefGoogle Scholar
  26. 26.
    Vermeer SE, Hollander M, van Dijk EJ, Hofman A, Koudstaal PJ, Breteler MM (2003) Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Stroke 34:1126–1129PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kazuei Igarashi
    • 1
    • 2
  • Keiko Kashiwagi
    • 3
  1. 1.Graduate School of Pharmaceutical SciencesChiba UniversityChibaJapan
  2. 2.Amine Pharma Research InstituteInnovation Plaza at Chiba UniversityChibaJapan
  3. 3.Faculty of PharmacyChiba Institute of ScienceChibaJapan

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