Mechanisms Underlying Physiological Functions of Food Factors <i>via</i> Non-specific Interactions with Biological Proteins

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  • Murakami Akira
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University

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Other Title
  • 生体タンパク質との非特異的な相互作用を介した食品成分の機能性発現機構
  • Symposium Review 生体タンパク質との非特異的な相互作用を介した食品成分の機能性発現機構
  • Symposium Review セイタイ タンパクシツ ト ノ ヒトクイテキ ナ ソウゴ サヨウ オ カイシタ ショクヒン セイブン ノ キノウセイ ハツゲン キコウ
  • Mechanisms Underlying Physiological Functions of Food Factors via Non-specific Interactions with Biological Proteins

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Abstract

  We previously reported that zerumbone, a sesquiterpene found in Zingiber zerumbet SMITH, showed notable cancer preventive effects in various organs of experimental rodents. This agent up-regulated nuclear factor-E2-related factor (Nrf2)-dependent expressions of anti-oxidative and xenobiotics-metabolizing enzymes, leading to an increased self-defense capacity. On the other hand, zerumbone markedly suppressed the expression of cyclooxygenase-2, an inducible pro-inflammatory enzyme, by disrupting mRNA stabilizing processes. Binding experiments using a biotin derivative of zerumbone demonstrated that Keap1, an Nrf2 repressive protein, is one of its major binding proteins that promotes their dissociation for inducing Nrf2 transactivation. We then generated a specific antibody against zerumbone-modified proteins and found that zerumbone modified numerous cellular proteins in a non-specific manner, with global distribution of the modified proteins seen not only in cytoplasm but also the nucleus. Based on those observations, zerumbone was speculated to cause proteo-stress, a notion supported by previous findings that it increased the C-terminus of Hsc70 interacting protein-dependent protein ubiquitination and also promoted aggresome formation. Interestingly, zerumbone counteracted proteo-stress and heat stress via up-regulation of the protein quality control systems (PQCs), e.g., heat shock proteins (HSPs), ubiquitin-proteasome, and autophagy. Meanwhile, several phytochemicals, including ursolic acid and curcumin, were identified as marked HSP70 inducers, whereas most nutrients tested were scarcely active. Recent studies have revealed that PQCs play important roles in the prevention of many lifestyle related diseases, such as cancer, thus non-specific binding of phytochemicals to cellular proteins may be a novel and unique mechanism underlying their physiological activities.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 135 (1), 47-55, 2015

    The Pharmaceutical Society of Japan

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