Digestive Diseases and Sciences

, Volume 47, Issue 12, pp 2799–2804 | Cite as

Induction of a 72-kDa Heat-Shock Protein in Cultured Rat Gastric Mucosal Cells and Rat Gastric Mucosa by Zinc l-Carnosine

  • Masaru Odashima
  • Michiro Otaka
  • Mario Jin
  • Noriaki Konishi
  • Toshihiro Sato
  • Sayuri Kato
  • Tamotsu Matsuhashi
  • Chieko Nakamura
  • Sumio Watanabe
Article

Abstract

An antiulcer drug, zinc l-carnosine (polaprezinc), provides gastric mucosal protection against various irritants. In this study, we evaluated the effects of zinc l-carnosine on expression of 72-kDa heat shock protein (HSP72, stress inducible HSP70), which is known as an endogenous cytoprotectant in a wide variety of cells, including rat gastric mucosa in vitro and in vivo. Expression of HSP72 after exposure to zinc l-carnosine, zinc sulfate, or l-carnosine (1–300 μM) in rat gastric mucosal cells (RGM1) and intragastric administration of zinc l-carnosine, zinc sulfate (30 or 100 mg/kg) and l-carnosine (76 mg/kg) was investigated by western blotting and densitometric analysis. Exposure to zinc l-carnosine and zinc sulfate increased the expression of HSP72 significantly in RGM1 cells. Intragastric administration of zinc l-carnosine and zinc sulfate showed significant increment in HSP72 in rat gastric mucosa also in vivo. The ability to induce HSP72 is significantly higher in zinc l-carnosine compared with zinc sulfate based on molecular concentration in vivo. However, l-carnosine did not increase the expression of HSP72 in vitro and in vivo. Zinc derivatives, especially zinc l-carnosine, could be a strong HSP72 (chaperon) inducer, which has been known to enhance mucosal protective ability.

heat shock protein zinc gastric mucosa mucosal protection 

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REFERENCES

  1. 1.
    Tissieres A, Mictchell HK, Tracy VM: Protein synthesis in salivary glands of Drosophilia melanogaster: Relation to chromosome puffs. J Mol Biol 84:384–393, 1974Google Scholar
  2. 2.
    Hightower LE: Cultured animal cells exposed to amino acid analogues or puromycin rapidly synthesize several polypeptides. J Cell Physiol. 102:407–427, 1980Google Scholar
  3. 3.
    Itoh H, Tashima Y: The stress (heat shock) proteins. Int J Biochem 23:1185–1191, 1991Google Scholar
  4. 4.
    Otaka M, Zeniya A, Fujimori S, Okuyama A, Jin M, Itoh S, Otani S, Iwabuchi A, Sasahara H, Tashima Y, Masamune O: Preinduction of a 72-kDa heat shock protein prevents HCl-induced gastric mucosal lesion. Gastroenterology 110:A219, 1996Google Scholar
  5. 5.
    Zeniya A, Otaka M, Itoh H, Kuwabara T, Fujimori S, Otani S, Tashima Y, Masamune O: Induction and intracellular localization of a 72-kDa heat shock protein in rat gastric mucosa after water-immersion stress. J Gastroenterol 30:572–577, 1995Google Scholar
  6. 6.
    Nakamura K, Rokutan K, Marui N, Aoike A, Kawai K: Induction of heat shock proteins and their implication in protection against ethanol-induced damage in cultured guinea pig gastric mucosal cells. Gastroenterology 101:161–166, 1991Google Scholar
  7. 7.
    Hatayama T, Asai Y, Wakatsuki T, Kitamura T, Imahara H: Regulation of hsp70 synthesis induced by cupric sulfate and zinc sulfate in thermotolerant HeLa cells. J Biochem 114:592–597, 1993Google Scholar
  8. 8.
    Bauman JW, Liu J, Klaassen CD: Production of metallothionein and heat shock proteins in response to metals. Fundam Appl Toxicol 21:15–22, 1993Google Scholar
  9. 9.
    Hatayama T, Tsukui Y, Wakatsuki T, Kitamura T, Imahara H: Characteristic induction of 70000 Da-heat shock protein and metallothionein by zinc in HeLa cells. Mol Cell Biochem 112:143–153, 1992Google Scholar
  10. 10.
    Klosterhalfen B, Töns C, Hauptmann S, Tietze L, Offner FA, Küpper W, Kirkpatrick CJ: Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogen aspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia. Biochem Pharmacol 52:1201–1210, 1996Google Scholar
  11. 11.
    Töns C, Klosterhalfen B, Klein HM, Rau HM, Anurov M, Oettinger A, Schumpelick V: Induction of heat shock protein 70 by zinc bis (DL-hydrogen aspartate) reduces ischemic smallbowel tissue damage in rats. Langenbecks Arch Chir 382:43–48, 1997Google Scholar
  12. 12.
    Pfeiffer CJ, Cho CH, Cheema A, Saltman D: Reserpineinduced gastric ulcers: Protection by lysosomal stabilization due to zinc. Eur J Pharmacol 61:347–353, 1980Google Scholar
  13. 13.
    Dupuy D, Szabo S: Protection by metals against ethanol induced gastric mucosal injury in rat. Comparative biochemical and pharmacologic studies implicate protein sulfhydryls. Gastroenterology 91:966–974, 1986Google Scholar
  14. 14.
    Seiki M, Ueki S, Tanaka Y, Soeda M, Hori Y, Aita H, Yoneta T, Morita H, Tagashira E, Okabe S: Studies on anti-ulcer effects of a new compound, zinc L-carnosine. Folia Pharmacol Jpn 95:257–269, 1990Google Scholar
  15. 15.
    Seiki M, Ueki S, Hori Y, Aita H, Yoneta T, Tagashira E: Effects of a new compound, Z-103 on various acute experimental models of gastric and duodenal lesions in rats. Ther Res 12:3243–3251, 1991Google Scholar
  16. 16.
    Arakawa T, Satoh H, Nakamura A, Nebiki H, Fukuda T, Sakuma H, Nakamura H, Ishikawa M, Seiki M, Kobayashi K: Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats. Dig Dis Sci 35:559–566, 1990Google Scholar
  17. 17.
    Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254, 1976Google Scholar
  18. 18.
    Otaka M, Itoh H, Kuwabara T, Zeniya A, Fujimori S, Otani S, Tashima Y, Masamune O: Induction of a 60-kDa heat shock protein in rat pancreas by water-immersion stress. Int J Biochem 25:1769–1773, 1993Google Scholar
  19. 19.
    Towbin H, Staehelin T, Gordon J: Electrophoreic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354, 1979Google Scholar
  20. 20.
    Gething MJ, Sambrook J: Protein folding in the cell. Nature 355:33–45, 1992Google Scholar
  21. 21.
    Rothman JE. Polypeptide chain binding proteins: Catalysts of protein folding and related processes in the cells. Cell 59:591–601, 1989Google Scholar
  22. 22.
    Jin M, Otaka M, Okuyama A, Itoh S, Otani S, Odashima M, Iwabuchi A, Konishi N, Wada I, Pacheco I, Itoh H, Tashima Y, Masamune O: Association of 72-kDa heat shock protein expression with adaptation to aspirin in rat gastric mucosa. Dig Dis Sci 44:1401–1407, 1999Google Scholar
  23. 23.
    Hamer DH: Metallothionein: Annu Rev Biochem 55:913–951, 1986Google Scholar
  24. 24.
    Kägi JHR, Schäffer A: Biochemistry of metallothionein. Biochemistry 27:8509–8515, 1988Google Scholar
  25. 25.
    Hiderbrand CE, Tobey RA, Campbel, EW, Enger MD: A cadmium-resistant variant of the Chinese hamster (CHO) cell with increased metallothionein induction capacity. Exp Cell Res 124:237–246, 1979Google Scholar
  26. 26.
    Karin M, Cathala G, Nguyen-Huu MC: Expression and regulation of a human metallothionein gene carried an autonomously replicating shuttle vector. Proc Natl Acad Sci USA 80:4040–4044, 1983Google Scholar
  27. 27.
    Ochi T, Otsuka F, Takahashi K, Osawa M: Glutathione and metallothioneins as cellular defense against cadmium toxicity in cultured Chinese hamster cells. Chem Biol Interact 65:1–14, 1988Google Scholar
  28. 28.
    Richards RI, Heguy A, Karin M: Structural and functional analysis of human metallothionein-IA gene: different induction by metal ions and glucocorticoid. Cell 37:263–272, 1984Google Scholar
  29. 29.
    Carter AD, Felber BK, Walling M, Jubier MF, Schmidt CJ, Hamer DH: Duplicated heavy metal control sequences of the mouse metallothionein-I gene. Proc Natl Acad Sci USA 81:7392–7396, 1984Google Scholar
  30. 30.
    Seguin C, Hamer DH: Regulation in vitro of metallothionein gene binding factors. Science 235:1383–1387, 1987Google Scholar
  31. 31.
    Westin G, Schaffner W: A zinc-responsive factor interacts with metal-regulated enhance (MRE) of the mouse metallothionein-I gene. EMBO J 7:3763–3770, 1988Google Scholar
  32. 32.
    Szczypka MS, Thiele DJ: A cysteine-rich nuclear protein activates yeast metallothionein gene transcription. Mol Cell Biol 9:421–429, 1989Google Scholar
  33. 33.
    Wu BJ, Kingston RE, Morimoto RI: Human hsp70 promoter contains at least two distinct regulatory domains. Proc Natl Acad Sci USA 83:529–633, 1986Google Scholar
  34. 34.
    Seiki M, Aita H, Mera Y, Arai K, Toyoma S, Furuta S, Morita H, Hori Y, Yoneta T, Tagashira E: The gastric mucosal adhesiveness of Z-103 in rats with chronic ulcer. Folia Pharmacol Jpn 99:255–263, 1992Google Scholar

Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Masaru Odashima
    • 1
  • Michiro Otaka
    • 1
  • Mario Jin
    • 1
  • Noriaki Konishi
    • 1
  • Toshihiro Sato
    • 1
  • Sayuri Kato
    • 1
  • Tamotsu Matsuhashi
    • 1
  • Chieko Nakamura
    • 1
  • Sumio Watanabe
    • 1
  1. 1.First Department of Internal MedicineAkita University School of MedicineAkitaJapan

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