Nitric Oxide Promotes Survival of Cerebral Cortex Neurons with Simultaneous Addition of [Fe(II)(β-Citryl-L-glutamate)] Complex in Primary Culture

スポンサーリンク

概要

• 論文の詳細を見る

• It has been reported that the activity of mitochondrial aconitase (m-aconitase) is rapidly inhibited in a variety of cells when exposed to nitric oxide (NO). In present study, we found that NO significantly increased the number of surviving neurons via enhanced mitochondrial functions with simultaneous addition of the [Fe(II)(β-citryl-<span style="font-variant: small-caps;">L</span>-glutamate; β-CG)] complex. In vitro, a variety of aconitase-inhibitors, such as fluorocitrate, cyanide ion, ferricyanide ([Fe(CN)6]), and various oxidants including superoxide anion, inhibited the activity of m-aconitase even in the presence of Fe(II), whereas a NO-donor, nitroprusside (SNP) ([Fe(CN)5NO]), was the only agent that significantly increased activity of that enzyme. Therefore, it is reasonable to assume that NO released from SNP promotes Fe-dependent activation of aconitase. All other tested NO-donors, including 3-morpholino-sydnonimine (SIN), Deta NONOate (NOC18), and NaNO2, also promoted activation of m-aconitase in time- and dose-dependent manners in the presence of Fe(II). The promoting effects of the NO-donors on activation disappeared with the addition of NO-scavengers. In intact mitochondria, all tested NO-donors promoted reactivation of aconitase in a dose-dependent manner in the presence of Fe(II), whereas that was not seen in its absence. These findings suggest that NO released from NO-donors promotes Fe-dependent activation of aconitase. In mixed neuronal and glial cultures, NO-donors except for SNP enhanced mitochondrial activity at low concentrations. Furthermore, simultaneous addition of the [Fe(II)(β-CG)] complex significantly enhanced those activities and greatly increased the number of surviving neurons. Thus, NO can carry Fe ions into m-aconitase via the guide of the tag of β-CG addressed to the enzyme.

著者

• Narahara Masanori

  Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University

• Hamada-Kanazawa Michiko

  Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University

• Miyake Masaharu

  Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University

• Tanaka Keiichi

  Laboratory Of Toxicology Graduate School Of Pharmaceutical Sciences Osaka University

• Takano Masaoki

  Department of Life Science Pharmacy, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University

• Min Kyong-Son

  Laboratory of Toxicology, Faculty of Pharmacy, Osaka Ohtani University

関連論文

• β-Citryl-L-glutamate Is an Endogenous Iron Chelator That Occurs Naturally in the Developing Brain
• Superoxide Scavenging and Xanthine Oxidase Inhibiting Activities of Copper–β-Citryl-L-glutamate Complex
• Expression of Low-Molecular-Weight Kininogen in Mouse Vascular Smooth Muscle Cells
• Tissue-Specific Expression of Rat Kininogen mRNAs
• Expression of Low-Molecular-Weight Kininogen mRNA in Human Fibroblast WI38 Cells
• Trend in Lead Content of Airborne Particles and Mass of PM10 in the Metropolitan Bangkok
• .BETA.-Citryl-L-glutamate Acts as an Iron Carrier to Activate Aconitase Activity
• Nitric Oxide Promotes Survival of Cerebral Cortex Neurons with Simultaneous Addition of [Fe(II)(β-Citryl-L-glutamate)] Complex in Primary Culture
• Sexual Dimorphism of Urine Angiotensinogen Excretion in the Rat.

スポンサーリンク