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Cathepsin B inhibition by Z-FA.FMK blocks TNF-a/D-GalN-induced oxidative damage through increasing antioxidant defence in the brain of mice

Year 2012, Volume: 71 Issue: 2, 85 - 93, 25.12.2012

Abstract

Cathepsin B is a cysteine lysosomal protease which takes place in many inflammatory diseases. Inflammatory
processes within the brain represent a potential pathogenetic factor in neurodegenerative diseases
and inhibiton of cathepsin B, which is an inflammation-related enzyme, can be a potential therapeutic
utility in neuroinflammatory diseases. Thus, we researched the effect of benzyloxycarbonyl-phenilalaninealanine
fluoromethylketone (Z-FA.FMK), which is a pharmacological inhibitor of cathepsin B, on tumour
necrosis factor-α (TNF-α) and D-galactosamine (D-GalN)-induced brain damage. Because oxidative
damage accompanies inflammatory processes we aimed to research the alteration in some markers of
oxidative damage and antioxidant defence system. For this investigation mice were treated with 700
mg/kg D-GalN and 15 μg/kg TNF-α one hour after administration with 8 mg/kg Z-FA.FMK. Treatment
with Z-FA.FMK before TNF-α/D-GalN injection resulted in decreased lipid peroxidation levels, while
catalase, superoxide dismutase, glutathione peroxidase, paraoxonase 1 activities and glutathione levels
were increased in the brain tissue of mice. These results showed that cathepsin B inhibition by Z-FA.
FMK could be a potential therapeutic utility in neuroinflammatory diseases because of its ability to
block TNF-α/D-GalN-induced oxidative damage by increasing antioxidant defence in the brain of mice.
Keywords: Benzyloxycarbonyl-Phenyl-Alanine-fluoromethylketone (Z-FA.FMK), Cathepsin B, Dgalactosamine,
Oxidative damage, Tumour necrosis factor-α (TNF-α).

References

  • Aebi H. (1984) Catalase in vitro. Methods in En- zymology, 105:121-126.
  • Andrews Z.B., Diano S., Horvath T.L. (2005) Mi- tochondrial uncoupling proteins in the CNS: in support of function and survival. Nature Review of Neuroscience, 6(11):829-840.
  • Bahr B.A., Bendiske J. (2002) The neuropathogenic contributions of lysosomal dysfunction. Journal of Neurochemistry, 83(3):481–489.
  • Beutler E. (1975) Glutathione in red cell metabo- lism. In: A mannual of biochemical methods. New York: Grune and Stratton.
  • Bohley P., Seglen P.O. (1992) Proteases and prote- olysis in the lysosome. Experientia, 48(2):151- 157.
  • Buck M.R., Karustis D.G., Day N.A., Honn K.V., Sloane B.F. (1992) Degradation of extracellular- matrix proteins by human cathepsin B from nor- mal and tumour tissues. Biochemical Journal, 282(Pt1):273-278.
  • Cardozo C., Padilla M.L., Choi H.S., Lesser M. (1992) Goblet cell hyperplasia in large intrapul- monary airways alter intratracheal injection of cathepsin B Inti hamsters. American Review of Respiratory Disease, 145(3):675-679.
  • Chapman H.A., Riese R.J., Shi G.P. (1997) Emerg- ing roles for cysteine proteases in human biol- ogy. Annual Review of Physiology,59:63-88.
  • Chrobot M., Szaflarska-Szczepanik A., Drewa G. (2000) Antioxidant defence in children with chronic viral hepatitis B and C. Medical Science Monitor, 6(4):713-718.
  • Dziewulska D., Mossakowski M.J. (2003) Cellular expression of tumor necrosis factor a and its receptors in human ischemic stroke. Clinical Neuropathology, 22(1):35-40.
  • El-Demerdash F.M. (2011) Lipid peroxidation, oxi- dative stress and acetylcholinesterase in rat brain exposed to organophosphate and pyrethroid insecticides. Food and Chemical Toxicology, 49(6):1346-1352.
  • Feuerstein G.Z., Wang X., Barone F.C. (1997) In- flammatory gene expression in cerebral ischemia and trauma. Potential new therapeutic targets. Annals of the New York Academy of Sciences, 825:179-193.
  • Furlong C.E., Richter R.J., Seidel S.L., Motulsky A.G. (1988) Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hy- drolysis of the insecticide metabolites chlorpy- rifos oxon and paraoxon. American Journal of Human Genetic, 43(3):230-238.
  • Guicciardi M.E., Deussing J., Miyoshi H., Bronk S.F., Svingen P.A., Peters C., Kaufmann S.H., Gores G.J. (2000) Cathepsin B contributes to TNF-alpha-mediated hepatocyte apop- tosis by promoting mitochondrial release of cytochrome c. Journal of Clinical Investiga- tion,106(9):1127–1137.
  • Halliwell B. (1994) Free radicals and antioxidants: A personal view. Nutrion Review, 52(8 Pt1): 253-265.
  • Halliwell B. (2006) Reactive species and antioxi- dants. Redox biology is a fundamental theme of aerobic life. Plant Physiology,141(2): 312-322.
  • Hashimoto Y., Kakegawa H., Narita Y., Hachiya Y., Hayakawa T., Kos J., Turk V., Katunuma N. (2001) Significance of cathepsin B accumu- lation in synovial fluid of rheumatoid artritis. Biochemical and Biophysical Research Com- munications, 282(2): 334-339.
  • Huang Y., Erdmann N., Peng H., Zhao Y., Zheng J. (2005) The role of TNF related apoptosis- inducing ligand in neurodegenerative diseases. Celllular and Molecular Immunology, 2(2): 113-122.
  • Jomova K., Vondrakova D., Lawson M., Valko M. (2010) Metals, oxidative stress and neurode- generative disorders. Molecular and Cellular Biochemistry, 345(1-2): 91-104.
  • Kono Y., Fridovich I. (1982) Superoxide radical inhibits catalase. Journal of Biological Chem- istry, 257(10):5751-5754.
  • Lawrence C.P., Kadioglu A., Yang A.L., Coward W.R., Chow S.C. (2006) The Cathepsin B In- hibitor, z-FA-FMK, Inhibits Human T Cell Pro- liferation In Vitro and Modulates Host Response to Pneumococcal Infection In Vivo. Journal of Immunology, 177(6): 3827–3836.
  • Ledwozyw A., Michalak J., Stepien A., Kadziolka A. (1986) The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atheroscle- rosis. Clinical Chimica Acta, 155(3): 275-283.
  • Leist M., Gantner F., Bohlinger I., Germann P.G., Tiegs G., Wendel A. (1994) Murine hepatocyte apoptosis induced in vitro and in vivo by TNF- alpha requires transcriptional arrest. Journal of Immunology,153(4): 1778-1788.
  • Li W., Nie S., Xie M., Yu Q., Chen Y., He M. (2011) Ganoderma atrum polysaccharide attenuates oxidative stress induced by D-galactose in mouse brain. Life Sciences, 88(15-16): 713-718.
  • Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J. (1951) Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1): 265-275.
  • Lv S., Song H.L., Zhou Y., Li L.X., Cui W., Wang W., Liu P. (2010) Tumor necrosis factor-a af- fects blood-brain barrier permeability and tight junction-associated occluding in acute liver fail- ure. Liver International, 30(8): 1198-1210.
  • Manna S.K., Zhang H.J., Yan T., Oberley L.W. and Aggarwal B.B. (1998) Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1. Journal of Biological Chemistry, 273(21): 13245–13254.
  • Meister A., Anderson M.E. (1983) Glutathione. Annual Review of Biochemistry, 52: 711-760.
  • Moreno I., Pichardo S., Jos A., Gomez-Amores L., Mate A., Vazquez C.M., Camean A.M. (2005) Antioxidant enzyme activity and lipid peroxi- dation in liver and kidney of rats exposed to microcystin-LR administered intraperitoneally. Toxicon, 45(4): 395-402.
  • Mylroie A.A., Collins H., Umbles C., Kyle J. (1986) Erythrocyte superoxide dismutase activity and other parameters of copper status in rats in- gesting lead acetate. Toxicology and Applied Pharmacology, 82(3): 512-520.
  • Nathan C. (2002) Points of control in inflammation. Nature, 420(6917): 846-852.
  • Navab M., Hama-Levy S., Van Lenten B.J., Fonar- rov G.C., Cardinez C.J., Castellani L.W., Bren- nan M.L., Lusis A.J., Fogelman A.M., La Du B.N. (1997) Mildy oxidized LDL induces an increases J /paraoxonase ratio. Journal of Clini- cal Investigation, 99(8): 2005-2019.
  • Negre-Salvayre A., Hirtz C., Carrera G., Cazenave R., Troly M., Salvayre R., Penicaud L., Casteilla L. (1997) A role for uncoupling protein-2 as a regulator of mitocondrial hydrogen peroxide generation. FASEB Journal, 11(10): 809-815.
  • Paglia D.E., Valentine W.N. (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory and Clinical Medicine, 70(1): 158-169.
  • Peng C., Chan H.Y., Li Y.M., Huang Y., Chen Z.Y. (2009) Black tea theaflavins extend the lifespan of fruit flies. Experimental Gerontology, 44(12): 773-83.
  • Rajaraman P., Hutchinson A., Rothman N., Black P.M., Fine H.A., Loeffler J.S., Selker R.G., Shapiro W.R., Linet M.S., Inskip D. (2008) Oxidative response gene polymorhisims and risk of adult brain tumors. Neuro Oncology, 10(5):709-715.
  • Sugino K., Dhi K., Yamada K., Kawasaki T. (1987) The role of lipid peroxidation in endotoxin- induced hepatic damage and the protective ef- fect of antioxidants. Surgery, 101(6): 846-752.
  • Tanaka S., Ide M., Shibutani T., Ohtaki H., Numazawa S., Shioda S., Yoshida T. (2006) Lipopolysaccharide-induced microglial acti- vation induces learning and memory deficits without neuronal cell death in rats. Journal of Neuroscience Research, 83(4): 557-566.
  • Trembovler V., Beit-Yannai E., Younis F., Gallily R., Horowitz M., Shohami E. (1999) Antioxi- dants attenuate acute toxicity of tumour necro- sis factor-alpha induced by brain injury in rat. Journal of Interferon and Cytokine Research, 19(7): 791-795.
  • Zdolsek J., Zhang H., Roberg K., Brunk U.T. (1993) H2O2-mediated damage to lysosomal mem- branes of J-774 cells. Free Radical Research Communication,18(2): 71–85.
  • Zhao M., Antunes F., Eaton J.W., Brunk U.T. (2003) Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. European Journal of Biochemistry, 270(18): 3778–3786.

Z-FA.FMK aracılığı ile katepsin B inhibisyonu fare beyninde TNF- α/D-GalN ile oluşturulan oksidatif hasarı antioksidan savunmayı artırarak engeller

Year 2012, Volume: 71 Issue: 2, 85 - 93, 25.12.2012

Abstract

Katepsin B birçok inflamatuvar hastalığın patolojisinde rol alan bir sistein proteazdır. Nörodejeneratif hastalıklarda beyindeki inflamatuvar süreçler potansiyel bir patojenik faktör olarak kabul edildiğinden, inflamasyon ile ilişkili bir enzim olan katepsin B’nin inhibisyonu nöroinflamatuvar hastalıklarda potansiyel bir tedavi yaklaşımı olabilir. Bu nedenle, katepsin B’nin farmakolojik bir inhibitörü olan olan benziloksikarbonil-fenilalanin-alanin-fluorometilketon (Z-FA.FMK)’un tümor nekroz faktor-α (TNF-α) ve D-galaktozamin (D-GalN) ile uyarılan beyin hasarı üzerine olan etkilerini araştırdık. Oksidatif hasar inflamatuvar süreçlere katıldığından, bazı oksidatif hasar ve antioksidan savunma göstergelerindeki değişimleri araştırmayı amaçladık. Bu araştırma için farelere 8 mg/kg Z-FA.FMK uygulanmasından 1 saat sonra 700 mg/kg D-GalN ve 15 µg/kg TNF-α enjekte edildi. TNF-α/D-GalN enjeksiyonundan önce Z-FA.FMK uygulanması fare beyin dokularında lipid peroksidasyon seviylerinin azalmasına karşın katalaz, superoksit dismutaz, glutatyon peroksidaz ve paraoksonaz 1 aktiviteleri ve glutatyon seviyelerinde artış ile sonuçlandı. Bu bulgular, Z-FA.FMK aracılığıyla katepsin B inhibisyonunun, fare beyninde TNF-α/D-GalN ile uyarılan oksidatif hasarı antioksidan savunmayı artırarak engellemesinden dolayı, nöroinflamatuvar hastalıklarda bir tedavi yaklaşımı olabileceğini göstermektedir.

References

  • Aebi H. (1984) Catalase in vitro. Methods in En- zymology, 105:121-126.
  • Andrews Z.B., Diano S., Horvath T.L. (2005) Mi- tochondrial uncoupling proteins in the CNS: in support of function and survival. Nature Review of Neuroscience, 6(11):829-840.
  • Bahr B.A., Bendiske J. (2002) The neuropathogenic contributions of lysosomal dysfunction. Journal of Neurochemistry, 83(3):481–489.
  • Beutler E. (1975) Glutathione in red cell metabo- lism. In: A mannual of biochemical methods. New York: Grune and Stratton.
  • Bohley P., Seglen P.O. (1992) Proteases and prote- olysis in the lysosome. Experientia, 48(2):151- 157.
  • Buck M.R., Karustis D.G., Day N.A., Honn K.V., Sloane B.F. (1992) Degradation of extracellular- matrix proteins by human cathepsin B from nor- mal and tumour tissues. Biochemical Journal, 282(Pt1):273-278.
  • Cardozo C., Padilla M.L., Choi H.S., Lesser M. (1992) Goblet cell hyperplasia in large intrapul- monary airways alter intratracheal injection of cathepsin B Inti hamsters. American Review of Respiratory Disease, 145(3):675-679.
  • Chapman H.A., Riese R.J., Shi G.P. (1997) Emerg- ing roles for cysteine proteases in human biol- ogy. Annual Review of Physiology,59:63-88.
  • Chrobot M., Szaflarska-Szczepanik A., Drewa G. (2000) Antioxidant defence in children with chronic viral hepatitis B and C. Medical Science Monitor, 6(4):713-718.
  • Dziewulska D., Mossakowski M.J. (2003) Cellular expression of tumor necrosis factor a and its receptors in human ischemic stroke. Clinical Neuropathology, 22(1):35-40.
  • El-Demerdash F.M. (2011) Lipid peroxidation, oxi- dative stress and acetylcholinesterase in rat brain exposed to organophosphate and pyrethroid insecticides. Food and Chemical Toxicology, 49(6):1346-1352.
  • Feuerstein G.Z., Wang X., Barone F.C. (1997) In- flammatory gene expression in cerebral ischemia and trauma. Potential new therapeutic targets. Annals of the New York Academy of Sciences, 825:179-193.
  • Furlong C.E., Richter R.J., Seidel S.L., Motulsky A.G. (1988) Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hy- drolysis of the insecticide metabolites chlorpy- rifos oxon and paraoxon. American Journal of Human Genetic, 43(3):230-238.
  • Guicciardi M.E., Deussing J., Miyoshi H., Bronk S.F., Svingen P.A., Peters C., Kaufmann S.H., Gores G.J. (2000) Cathepsin B contributes to TNF-alpha-mediated hepatocyte apop- tosis by promoting mitochondrial release of cytochrome c. Journal of Clinical Investiga- tion,106(9):1127–1137.
  • Halliwell B. (1994) Free radicals and antioxidants: A personal view. Nutrion Review, 52(8 Pt1): 253-265.
  • Halliwell B. (2006) Reactive species and antioxi- dants. Redox biology is a fundamental theme of aerobic life. Plant Physiology,141(2): 312-322.
  • Hashimoto Y., Kakegawa H., Narita Y., Hachiya Y., Hayakawa T., Kos J., Turk V., Katunuma N. (2001) Significance of cathepsin B accumu- lation in synovial fluid of rheumatoid artritis. Biochemical and Biophysical Research Com- munications, 282(2): 334-339.
  • Huang Y., Erdmann N., Peng H., Zhao Y., Zheng J. (2005) The role of TNF related apoptosis- inducing ligand in neurodegenerative diseases. Celllular and Molecular Immunology, 2(2): 113-122.
  • Jomova K., Vondrakova D., Lawson M., Valko M. (2010) Metals, oxidative stress and neurode- generative disorders. Molecular and Cellular Biochemistry, 345(1-2): 91-104.
  • Kono Y., Fridovich I. (1982) Superoxide radical inhibits catalase. Journal of Biological Chem- istry, 257(10):5751-5754.
  • Lawrence C.P., Kadioglu A., Yang A.L., Coward W.R., Chow S.C. (2006) The Cathepsin B In- hibitor, z-FA-FMK, Inhibits Human T Cell Pro- liferation In Vitro and Modulates Host Response to Pneumococcal Infection In Vivo. Journal of Immunology, 177(6): 3827–3836.
  • Ledwozyw A., Michalak J., Stepien A., Kadziolka A. (1986) The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atheroscle- rosis. Clinical Chimica Acta, 155(3): 275-283.
  • Leist M., Gantner F., Bohlinger I., Germann P.G., Tiegs G., Wendel A. (1994) Murine hepatocyte apoptosis induced in vitro and in vivo by TNF- alpha requires transcriptional arrest. Journal of Immunology,153(4): 1778-1788.
  • Li W., Nie S., Xie M., Yu Q., Chen Y., He M. (2011) Ganoderma atrum polysaccharide attenuates oxidative stress induced by D-galactose in mouse brain. Life Sciences, 88(15-16): 713-718.
  • Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J. (1951) Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1): 265-275.
  • Lv S., Song H.L., Zhou Y., Li L.X., Cui W., Wang W., Liu P. (2010) Tumor necrosis factor-a af- fects blood-brain barrier permeability and tight junction-associated occluding in acute liver fail- ure. Liver International, 30(8): 1198-1210.
  • Manna S.K., Zhang H.J., Yan T., Oberley L.W. and Aggarwal B.B. (1998) Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1. Journal of Biological Chemistry, 273(21): 13245–13254.
  • Meister A., Anderson M.E. (1983) Glutathione. Annual Review of Biochemistry, 52: 711-760.
  • Moreno I., Pichardo S., Jos A., Gomez-Amores L., Mate A., Vazquez C.M., Camean A.M. (2005) Antioxidant enzyme activity and lipid peroxi- dation in liver and kidney of rats exposed to microcystin-LR administered intraperitoneally. Toxicon, 45(4): 395-402.
  • Mylroie A.A., Collins H., Umbles C., Kyle J. (1986) Erythrocyte superoxide dismutase activity and other parameters of copper status in rats in- gesting lead acetate. Toxicology and Applied Pharmacology, 82(3): 512-520.
  • Nathan C. (2002) Points of control in inflammation. Nature, 420(6917): 846-852.
  • Navab M., Hama-Levy S., Van Lenten B.J., Fonar- rov G.C., Cardinez C.J., Castellani L.W., Bren- nan M.L., Lusis A.J., Fogelman A.M., La Du B.N. (1997) Mildy oxidized LDL induces an increases J /paraoxonase ratio. Journal of Clini- cal Investigation, 99(8): 2005-2019.
  • Negre-Salvayre A., Hirtz C., Carrera G., Cazenave R., Troly M., Salvayre R., Penicaud L., Casteilla L. (1997) A role for uncoupling protein-2 as a regulator of mitocondrial hydrogen peroxide generation. FASEB Journal, 11(10): 809-815.
  • Paglia D.E., Valentine W.N. (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory and Clinical Medicine, 70(1): 158-169.
  • Peng C., Chan H.Y., Li Y.M., Huang Y., Chen Z.Y. (2009) Black tea theaflavins extend the lifespan of fruit flies. Experimental Gerontology, 44(12): 773-83.
  • Rajaraman P., Hutchinson A., Rothman N., Black P.M., Fine H.A., Loeffler J.S., Selker R.G., Shapiro W.R., Linet M.S., Inskip D. (2008) Oxidative response gene polymorhisims and risk of adult brain tumors. Neuro Oncology, 10(5):709-715.
  • Sugino K., Dhi K., Yamada K., Kawasaki T. (1987) The role of lipid peroxidation in endotoxin- induced hepatic damage and the protective ef- fect of antioxidants. Surgery, 101(6): 846-752.
  • Tanaka S., Ide M., Shibutani T., Ohtaki H., Numazawa S., Shioda S., Yoshida T. (2006) Lipopolysaccharide-induced microglial acti- vation induces learning and memory deficits without neuronal cell death in rats. Journal of Neuroscience Research, 83(4): 557-566.
  • Trembovler V., Beit-Yannai E., Younis F., Gallily R., Horowitz M., Shohami E. (1999) Antioxi- dants attenuate acute toxicity of tumour necro- sis factor-alpha induced by brain injury in rat. Journal of Interferon and Cytokine Research, 19(7): 791-795.
  • Zdolsek J., Zhang H., Roberg K., Brunk U.T. (1993) H2O2-mediated damage to lysosomal mem- branes of J-774 cells. Free Radical Research Communication,18(2): 71–85.
  • Zhao M., Antunes F., Eaton J.W., Brunk U.T. (2003) Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. European Journal of Biochemistry, 270(18): 3778–3786.
There are 41 citations in total.

Details

Primary Language English
Journal Section Makaleler
Authors

Selda Gezginci-oktayoglu This is me

İsmet Burcu Turkyilmaz This is me

Refiye Yanardag This is me

Sehnaz Bolkent This is me

Publication Date December 25, 2012
Submission Date December 25, 2012
Published in Issue Year 2012 Volume: 71 Issue: 2

Cite

AMA Gezginci-oktayoglu S, Burcu Turkyilmaz İ, Yanardag R, Bolkent S. Cathepsin B inhibition by Z-FA.FMK blocks TNF-a/D-GalN-induced oxidative damage through increasing antioxidant defence in the brain of mice. Eur J Biol. November 2012;71(2):85-93.