type: misc

label: url

en: The importance of hexokinase in the energy metabolism of tumor cells

ja: ヘキソキナーゼとがんの代謝

en: Experimental Medicine

ja: 実験医学


en: The mechanisms of the release of cytochrome C from mitochondria revealed by proteomics analysis.

en: Mitochondrial permeability transition (PT) is the phenomenon in which the mitochondrial inner membrane becomes permeable to various solutes and ions. When PT is induced by Ca(2+), cytochrome c is released from mitochondria into the cytosol where it then triggers subsequent steps of programmed cell death, apoptosis. Thus, the proteins that regulate PT and cytochrome c release could become druggable targets for various diseases. However, the mechanisms of PT and the release of cytochrome c have not yet been revealed. We previously showed that valinomycin, a potassium selective ionophore, also caused release of cytochrome c from mitochondria without inducing PT. This result indicates that cytochrome c could be released from mitochondria with or without induction of PT. In this study, to understand the difference of effects of valinomycin and Ca(2+) on mitochondria, we examined what protein species are released from valinomycin- and Ca(2+)-treated mitochondria by LC-MS/MS. As a result, only the proteins located in the intermembrane space were found to be released from valinomycin-treated mitochondria, while those in both the intermembrane space and in the matrix were released from Ca(2+)-treated mitochondria. Furthermore, the protein releases by each reagent occurred not selectively but in a concentration-dependent manner. Based on these results, the permeabilization effects of Ca(2+) and valinomycin on the inner and outer mitochondrial membranes are discussed.

en: Journal of the Pharmaceutical Society of Japan


en: ミトコンドリアをターゲットとするアポトーシス阻害剤

ja: ミトコンドリアをターゲットとするアポトーシス阻害剤

en: 化学と生物

ja: 化学と生物


en: プロテオミクスで探るミトコンドリアからのシトクロムc漏出機構

ja: プロテオミクスで探るミトコンドリアからのシトクロムc漏出機構

en: Seibutsu Butsuri

ja: 生物物理


en: Structural and Functional Properties of the C-terminal Region of Mitochondrial ADP/ATP Carrier

ja: ミトコンドリア内膜のADP/ATP透過担体のC末端領域の構造特性と機能

en: Mitochondrial ADP/ATP carrier (AAC) is a protein catalyzing the transport of adenine nucleotides across inner mitochondrial membrane. In this review article, we first briefly introduce structural and functional properties of this protein. Next, we describe the results of our recent studies on the difference in the C-terminal region between yeast type 2 AAC isoform and bovine type 1 AAC isoform. Furthermore, based on the reactivities of cysteine residues that replaced amino acids in the sixth transmembrane segment, the probable structural features of the C-terminal region of this carrier are discussed.

ja: 薬学雑誌


en: Cold-induced changes in gene expression in brown adipose tissue: implications for the activation of thermogenesis.

en: Brown adipose tissue (BAT) is the site of heat production (thermogenesis). This unique function is performed by uncoupling protein 1 (UCP1) specifically expressed in mitochondria of BAT. UCP1 dissipates the driving force of ATP synthesis, and thus causes heat production followed by energy expenditure. The thermogenic function of BAT has the role of maintaining body temperature under cold conditions. When animals are exposed to cold, the expression of UCP1 gene is increased to activate thermogenesis. To date, functional analysis of BAT has been focused on UCP1, because it plays an indispensable role in thermogenesis. However, the gene expression of not only UCP1 but also that of other genes in BAT is expected to be regulated to achieve effective thermogenesis. Our previous investigations showed increased expression of genes that encode several energy metabolic enzymes in the BAT of rats kept in the cold. These changes in gene expression imply that the enhancement of energy metabolism is needed to activate thermogenesis. Furthermore, various reports from studies focused on genes whose expression is changed in response to cold stimulation have provided new insights into the function of BAT. In this review, to understand the thermogenic function of BAT systematically, we have provided an overview of previous findings on changes in the expression of genes thought to be related to the activation of thermogenesis in BAT.

en: Biological & Pharmaceutical Bulletin

ja: Biological & Pharmaceutical Bulletin


en: Exploratory Studies on Biomarkers : An Example Study on Brown Adipose Tissue

ja: バイオマーカーの探索:褐色脂肪組織に関する研究事例

en: In mammals, two kinds of adipose tissue are known to exist, i.e., white (WAT) and brown (BAT) adipose tissue. The physiological role of WAT is storage of excess energy as fat, whereas that of BAT is the expenditure of excess energy as heat. The uncoupling protein UCP1, which is specifically expressed in brown fat mitochondria, dissipates the proton electrochemical potential across the inner mitochondrial membrane, known as a driving force of ATP synthesis, and thus it dissipates excess energy in a form of heat. Because deficiency in effective expenditure of excess energy causes accumulation of this energy in the form of fat (i.e., obesity), it is very important to understand the energy metabolism in this tissue for the development of anti-obesity drugs. In this article, in addition to providing a brief introduction to the functional properties of BAT and UCP1, the results of our exploratory studies on protein components involved in the energy-dissipating function in BAT.

en: IEEJ Transactions on Electronics, Information and Systems

ja: 電気学会論文誌C (電子，情報，システム部門誌)


en: Drug-Induced Gingival Overgrowth a Review

en: Drug-induced gingival overgrowth is a side effect associated with 3 types of drugs: anticonvulsants (phenytoin), immunosuppressive agents (cyclosporine A), and various calcium channel blockers for cardiovascular diseases. Gingival overgrowth is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components with various degrees of inflammation. Although the mechanisms of these disorders have not been elucidated, recent studies suggest that these disorders seem to be induced by the disruption of homeostasis of collagen synthesis and degradation in gingival connective tissue, predominantly through the inhibition of collagen phagocytosis of gingival fibroblasts. The integrins are a large family of heterodimeric transmembrane receptors for extracellular matrix molecules. alpha2beta1 integrin serves as a specific receptor for type I collagen on fibroblasts, and alpha2 integrin has been shown to play a crucial role in collagen phagocytosis. Actin filaments, which are assembled from monomers and oligomers, are involved in collagen internalization after binding to integrins. Furthermore, the implication of intracellular calcium in the regulation of integrin-mediated binding activity and gelsolin activity, known as a calcium-dependent actin-severing protein, is also described. In this review, we focus on collagen metabolism in drug-induced gingival overgrowth, focusing on the regulation of collagen phagocytosis in fibroblasts.


en: Identification of possible protein machinery involved in the thermogenic function of brown adipose tissue.

en: Brown adipose tissue (BAT) is believed to function by dissipating excess energy in mammals. It is very important to understand the energy metabolism held in BAT since disorder of its energy-dissipating function may cause obesity or lifestyle-related diseases such as hypertension and diabetes. This function in BAT is mainly attributable to uncoupling protein (UCP), specifically expressed in its mitochondria. This protein consumes excess energy as heat by dissipating the H+ gradient across the inner mitochondrial membrane that is utilized as a driving force for ATP synthesis. In this review article, in addition to providing a brief introduction to the functional properties of BAT and UCP, we also describe and discuss properties of cultured brown adipocytes and the results of our exploratory studies on protein components involved in the energy-dissipating function in BAT.

en: The Journal of Medical Investigation : JMI


en: Recent Progress in Studies on The Uncouplers of Oxidative Phosphorylation.

ja: 脱共役剤研究の最近の進歩

en: The chemical energy of nutrient molecules is converted in to ATP during the process of oxidative phosphorylation in mitochondria. Since the electrochemical potential gradient of H+ formed across the inner mitochondrial membrane by the oxidation of respiratory substrates is utilized as a driving force for ATP synthesis, the mitochondrial inner membrane is highly impermeable to H+. An increase in the permeability of this membrane to H+ causes inhibition of ATP synthesis, and chemicals that cause such an increase are called uncouplers. Ordinary known uncouplers are hydrophobic weak acids and show their activity by acting as protonophores. On the contrary, in recent studies, a variety of chemicals were found to act as uncouplers, not by acting as a protonophore, but by inducing permeability transition of the inner mitochondrial membrane or by inducing molecular ``slippage'' of the primary H+ pump. In this review article, recent progress made from studies on the uncouplers of oxidative phosphorylation is presented and discussed.

en: MEMBRANE

ja: 膜


en: Bioenergetics in brown adipose tissue.

ja: Bioenergetics in brown adipose tissue.

en: Recent Res. Devel.Bioener.

ja: Recent Res. Devel.Bioener.


en: Quantitative studies on the nuclear transport of plasmid DNA and gene expression employing nonviarl vectors

en: Advanced Drug Delivery Reviews

ja: Advanced Drug Delivery Reviews


en: Intracellular control of gene trafficking using liposomes as drug carriers

en: The objective of this review is to summarize some of the critical barriers in gene delivery and recent progress in overcoming such barriers using non-viral carrier systems. Receptor-mediated endocytosis is generally considered to be a principal entering pathway. Therefore, endosomal escape is an essential step for achieving efficient transfection. The nuclear membrane is also a critical barrier in gene delivery and the application of the nuclear localization signal is discussed, based on recent strategies. It is essential to optimize the carrier system, in order to enhance the transfection ability equivalent to a viral system. The importance of developing an intracellular pharmacokinetic model of genes is emphasized in the optimization of non-viral carrier systems.

en: European Journal of Pharmaceutical Sciences


en: Intracellular control of macromolecules by use of liposomes as drug carriers

en: Journal of Biological Macromolecules

ja: Journal of Biological Macromolecules


en: がん細胞の糖代謝を特異的に担うヘキソキナーゼの同定とその機能解析

ja: がん細胞の糖代謝を特異的に担うヘキソキナーゼの同定とその機能解析

en: Journal of the Pharmaceutical Society of Japan


en: キャリアによる細胞内デリバリー戦略と今後の課題

ja: キャリアによる細胞内デリバリー戦略と今後の課題

en: Drug Delivery System

ja: Drug Delivery System


en: ミトコンドリア輸送タンパクスーパーファミリー

ja: ミトコンドリア輸送タンパクスーパーファミリー

en: 生体の科学

ja: 生体の科学