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Decline in glutathione peroxidase activity is a reason for brain senescence: consumption of green tea catechin prevents the decline in its activity and protein oxidative damage in ageing mouse brain

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Abstract

The accumulation of oxidative damage is believed to contribute to senescence. We have previously found that the consumption of green tea catechins (GT-catechin), which are potent antioxidants, decreases oxidative damage to DNA and improves brain function in aged mice with accelerated senescence (SAMP10 mice). To investigate the mechanisms underlying the beneficial effects of GT-catechin, we measured the activities of antioxidative enzymes in the brains of aged SAMP10 mice. The activity of glutathione peroxidase (GPx), an essential enzyme for reduction of hydrogen and lipid peroxides, was significantly lower in aged mice than in younger ones. However, the decline in activity was prevented in aged mice that had consumed GT-catechin. The increased level of carbonyl proteins, a marker of oxidative damage in proteins, was also significantly reduced in aged mice that had consumed GT-catechin. The activities of superoxide dismutase and catalase were not decreased in aged mice. These results suggest that decreased activity of GPx importantly contributes to brain dysfunction in ageing SAMP10 mice. Furthermore, the intake of GT-catechin protected the decline in GPx activity and age-related oxidative damage in the brain.

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Abbreviations

ECG:

(−)-Epicatechin gallate

EGC:

(−)-Epigallocatechin

EGCG:

(−)-Epigallocatechin gallate

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GSH:

Reduced glutathione

GSSG:

Glutathione disulfide

GT-catechin:

Green tea catechins

NO:

Nitric oxide

ROS:

Reactive oxygen species

SAMP10:

A mouse strain with accelerated senescence

SAMR1:

Senescence-resistant inbred strain

SNAP:

S-nitro-N-acetyl-DL- penicillamine

SOD:

Superoxide dismutase

TCA:

Trichloroacetic acid

References

  • Aebi H (1984) Catalase in vitro. Meth Enzymol 105:121–126

    PubMed  CAS  Google Scholar 

  • Asahi M, Fujii J, Suzuki K, Seo HG, Kuzuya T, Hori M, Tada M, Fujii S, Taniguchi N (1995) Inactivation of glutathione peroxidase by nitric oxide. J Biol Chem 270:21035–21039

    Article  PubMed  CAS  Google Scholar 

  • Asahi M, Fujii J, Takao T, Kuzuya T, Hori M, Shimonishi Y, Taniguchi N (1997) The oxidation of selenocysteine is involved in the inactivation of glutathione peroxidase by nitric oxide donor. J Biol Chem 272:19152–19157

    Article  PubMed  CAS  Google Scholar 

  • Baud O, Greene AE, Li J, Wang H, Volpe JJ, Rosenberg PA (2004) Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes. J Neurosci 24:1531–1540

    Article  PubMed  CAS  Google Scholar 

  • Crack PJ, Taylor JM, Flentjar NJ, de Haan J, Hertzog P, Lannello RC, Kola I (2001) Increased infarct size and exacerbated apoptosis in the glutathione peroxidase-1 (Gpx-1) knockout mouse brain in response to ischemia/reperfusion injury. J Neurochem 78:1389–1399

    Article  PubMed  CAS  Google Scholar 

  • de Haan JB, Bladier C, Griffiths P, Kelner M, O’Shea RD, Cheung NS, Bronson RT, Silvestro MJ, Wild S, Zheng SS, Beart PM, Hertzog PJ, Kola I (1998) Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. J Biol Chem 273:22528–22536

    Article  PubMed  Google Scholar 

  • Devi SA, Kiran TR (2004) Regional responses in antioxidant system to exercise training and dietary Vitamin E in aging rat brain. Neurobiol Aging 25:501–508

    Article  PubMed  CAS  Google Scholar 

  • Dringen R, Pawlowski PG, Hirrlinger J (2005) Peroxide detoxification by brain cells. J Neurosci Res 79:157–165

    Article  PubMed  CAS  Google Scholar 

  • Foster TC (2006) Biological markers of age-related memory deficits: treatment of senescent physiology. CNS Drugs 20:153–166

    Article  PubMed  Google Scholar 

  • Ho Y-S, Magnenat J-L, Bronson RT, Cao J, Gargano M, Sugawara M, Funk CD (1997) Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem 272:16644–16651

    Article  PubMed  CAS  Google Scholar 

  • Kashima M. (1999) Effects of catechins on superoxide and hydroxyl radical. Chem Pharm Bull 47:279–283

    PubMed  CAS  Google Scholar 

  • Kidd PM (2005) Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative managements. Altern Med Rev 10:268–293

    PubMed  Google Scholar 

  • Kimura M, Umegaki K, Kasuya Y, Sugusawa A, Higuchi M. (2002) The relation between single/double or repeated tea catechin ingestions and plasma antioxidant activity in humans. Eur J Clin Nutr 56:1186–1193

    Article  PubMed  CAS  Google Scholar 

  • Levites Y, Weinreb O, Maor G, Youdim MBH, Mandel S. (2001) Green tea polyphenol (−)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. J Neurochem 78:1073–1082

    Article  PubMed  CAS  Google Scholar 

  • Liddell JR, Hoepken HH, Crack PJ, Robinson SR, Dringen R (2006) Glutathione peroxidase 1 and glutathione are required to protect mouse astrosytes from Iron-mediated hydrogen peroxide toxicity. J Neurosci Res 84:578–586

    Article  PubMed  CAS  Google Scholar 

  • Lindenau J, Noack H, Asayama K, Wolf G (1998) Enhanced cellular glutathione peroxidase immuno reactivity in activated astrosytes and in microglia during excitotoxine induced neurogeneration. Glia 24:252–256

    Article  PubMed  CAS  Google Scholar 

  • Maier CM, Chen PH (2002) Role of superoxide dismutases in oxidative damage and neurodegenerative disorders. Neuroscientist 8:323–334

    Article  PubMed  CAS  Google Scholar 

  • Nagai K, Jiang MHJ, Hada J, Nagata T, Yajima Y, Yamamoto S, Nishizaki T (2002) (−)-Epigallocatechin gallate protects against NO stress-induced neuronal damage after ischemia by acting as an anti-oxidant. Brain Res 965:319–322

    Article  Google Scholar 

  • Nakamura A, Goto S (1996) Analysis of protein carbonyls with 2,4-dinitrophenyl hydrazine and its antibodies by immunoblot in two dimensional gel electrophoresis. J Biochem 119:768–774

    PubMed  CAS  Google Scholar 

  • Nanjo F, Mori M, Goto K, Hara Y. (1999) Radical scavenging activity of tea catechins and their related compounds. Biosci Biotechnol Biochem 63:1621–1623

    Article  PubMed  CAS  Google Scholar 

  • Numata T, Saito T, Maekawa K, Takahashi Y, Saitoh H, Hosokawa T, Fujita H, Kurasaki M (2002) Bcl-2-linked apoptosis due to increase in NO synthetase in brain of SAMP10. Biochem Biophys Res Commn 297:517–522

    Article  CAS  Google Scholar 

  • Reznick AZ, Packer RL (1994) Oxidative damage to proteins: spectrophotometric methods for carbonyl assay. Meth Enzymol 233:357–363

    Article  PubMed  CAS  Google Scholar 

  • Sanz A, Caro P, Ibañez J, Gómez J, Gredilla R, Barja G (2005) Dietary restriction at old age lowers mitochondrial oxygen radical production and leak at complex I and oxidative DNA damage in rat brain. J Bioenerg Biomembr 37:83–90

    Article  PubMed  CAS  Google Scholar 

  • Schulz JB, Lindenau J, Seyfried J, Dichgans J (2000) Glutathione, oxidative stress and neurodegeneration. Eur J Biochem. 267:4904–4911

    Article  PubMed  CAS  Google Scholar 

  • Serrano F, Klann E (2004) Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res Rev 3:431–443

    Article  PubMed  CAS  Google Scholar 

  • Shimada A (1999) Age-dependent cerebral atrophy and cognitive dysfunction in SAMP10 mice. Neurobiol Aging 20:125–136

    Article  PubMed  CAS  Google Scholar 

  • Shimada A, Keino H, Satoh M, Kishikawa M, Hosokawa M (2003) Age-related loss of synapses in the frontal cortex of SAMP10 mouse: a model of cerebral degeneration. Synapse 48:198–204

    Article  PubMed  CAS  Google Scholar 

  • Shimada A, Keino H, Satoh M, Kishikawa M, Seriu N, Hosokawa M (2002) Age-related progressive neuronal DNA damage associated with cerebral degeneration in a mouse model of accelerated senescence. J Gerontol: Biol Sci Med Sci 57:B415–B421

    Google Scholar 

  • Skrzydlewska E, Ostrowska J, Farbiszewski R, Michalak K. (2002) Protective effect of green tea against lipid peroxidation in the rat liver, blood serum and the brain. Phytomedicine 9:232–238

    Article  PubMed  CAS  Google Scholar 

  • Skrzydlewska E, Augustyniak A, Michalak K, Farbiszewski R (2005) Green tea supplementation in rats of different ages mitigates ethanol-induced changes in brain antioxidant abilities. Alcohol 37:89–98

    Article  PubMed  CAS  Google Scholar 

  • Suzuki M, Mabuchi M, Ikeda M, Umegaki K, Tomita T (2004) Protective effect of green tea catechins on cerebral ischemic damage. Med Sci Monit 10:BR166–BR174

    PubMed  CAS  Google Scholar 

  • Taylor JM, Ali U, Iannelo RC, Hertzog P, Crack PJ (2005) Diminished Akt phosphorylation in neurons lacking glutathione peroxidase-1 (GPx1) leads to increase susceptibility to oxidative stress-induced cell death. J Neurochem 92:283–293

    Article  PubMed  CAS  Google Scholar 

  • Terao J (1999) Dietary flavonoids as antioxidants in vivo: conjugated metabolites of (−)-epicatechin and quercetin participate in antioxidative defense in blood plasma. J Med Invest 46:159–168

    PubMed  CAS  Google Scholar 

  • Unno K, Takabayashi F, Kishido T, Oku N. (2004) Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10). Exp Gerontol 39:1027–1034

    Article  PubMed  CAS  Google Scholar 

  • Unno K, Takabayashi F, Yoshida H, Choba D, Fukutomi R, Kikunaga N, Kishido T, Oku N, Hoshino M (2006) Daily consumption of green tea catechin delays memory regression in aged mice. Biogerontology, Epub. Sept. 7

  • Wei I-H, Wu Y-C, Wen C-Y, Shieh J-Y (2004) Green tea polyphenol (−)-epigallocatechin gallate attenuates the neuronal NADPH-d/n NOS expression in the nodose ganglion of acute hypoxic rats. Brain Res 999:73–80

    Article  PubMed  CAS  Google Scholar 

  • Zhu Y, Cavey PM, Ling Z (2006) Age-related changes in glutathione and glutathione-related enzymes in rat brain. Brain Res 1090:35–44

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan

    Takahiro Kishido & Naoto Oku

  2. Laboratory of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan

    Keiko Unno, Hirotoshi Yoshida, Daisuke Choba, Rie Fukutomi, Shunsuke Asahina, Kazuaki Iguchi & Minoru Hoshino

Authors
  1. Takahiro Kishido
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  2. Keiko Unno
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  3. Hirotoshi Yoshida
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  4. Daisuke Choba
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  5. Rie Fukutomi
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  6. Shunsuke Asahina
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  7. Kazuaki Iguchi
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  8. Naoto Oku
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  9. Minoru Hoshino
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Correspondence to Keiko Unno.

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Kishido, T., Unno, K., Yoshida, H. et al. Decline in glutathione peroxidase activity is a reason for brain senescence: consumption of green tea catechin prevents the decline in its activity and protein oxidative damage in ageing mouse brain. Biogerontology 8, 423–430 (2007). https://doi.org/10.1007/s10522-007-9085-7

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  • DOI: https://doi.org/10.1007/s10522-007-9085-7

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