ATF6alpha promotes astroglial activation and neuronal survival in a chronic mouse model of Parkinson\u27s disease.

13301甲第4001号博士（医学）金沢大学博士論文本文Full 以下に掲載：PLOS ONE 7(10) pp.e47950-e47950 2012. Public Library of Science. 共著者： Koji Hashida, Yasuko Kitao, Hirofumi Sudo, Yoshitaka Awa, Shinichiro Maeda, Kazutoshi Mori, Ryosuke Takahashi, Munekazu Iinuma, Osamu Hori

Photosynthetic physiology and primary productivity of phytoplankton in the Australian sector of the Southern Ocean

第2回極域科学シンポジウム　共通セッション「海氷圏の生物地球化学」 11月16日（水） 統計数理研究所 3階セミナー

α-Lipoic acid (LA) enantiomers protect SH-SY5Y cells against glutathione depletion

Growing evidence suggests that α-lipoic acid (LA) has neuroprotective effects in various pathological conditions including brain ischemia and neurodegeneration. While anti-oxidative activity has been thought to play a central role in LA-mediated neuroprotection, the precise mechanism and the effect of LA enantiomers (R- and S-LA) are not fully clarified. We, therefore, estimated the neuroprotective effects of LA against different cellular stresses including oxidative stress, endoplasmic reticulum (ER) stress and proteolytic stress using human neuroblastoma SH-SY5Y cells. All types of LAs (racemate, R-LA and S-LA) most effectively prevented cell death induced by buthionine sulfoximine (BSO) which depletes intracellular glutathione. Although direct effects of LA on glutathione depletion or generation of the reactive oxygen species (ROS) were relatively small upon BSO treatment, LA enhanced expressions of anti-oxidative genes such as heme oxygenase-1 (HO-1) and phase II detoxification enzymes such as NAD(P)H:Quinone Oxidoreductase 1 (NQO1). An inhibitor of NQO1, but not that of HO-1, suppressed LA-mediated protection against BSO. Further experiments revealed that all types of LAs activated cell survival-associated kinase Akt, and an inhibitor of PI3K, LY294002, suppressed both LA-induced upregulation of NQO1 and cell protection against BSO. Our results suggest an important role of PI3K/Akt-mediated upregulation of genes including phase II enzymes such as NQO1 in LA-mediated neuroprotection. © 2011 Elsevier B.V

The effect of Ndrg2 expression on astroglial activation

N-myc downstream-regulated gene 2 (Ndrg2) is a differentiation- and stress-associated molecule predominantly expressed in astrocytes in the central nervous system (CNS). To study the expression and possible role of Ndrg2 in quiescent and activated astrocytes, mice were administrated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP), a Parkinson disease (PD)-related neurotoxin which causes both neurodegeneration and glial activation. Immunohistological analysis revealed that Ndrg2 was highly expressed in both types of astrocytes, but less so in astrocytes during the early process of activation. Ndrg2 was also expressed in astrocyte-like cells, but not in neurons, in human brains from PD and Cortico-basal degeneration (CBD) patients. In cultured astrocytes, gene silencing of Ndrg2 significantly enhanced the numbers of 5-bromo-2′-deoxy-uridine (BrdU)-incorporated and proliferating cell nuclear antigen (PCNA)-positive cells, and reduced the length of cell processes and the amount of F-actin. In contrast, adenovirus-mediated overexpression of Ndrg2 significantly reduced the numbers of BrdU-incorporated and PCNA-positive cells, and enhanced the amount of F-actin. Fractionation and immunocytochemical analysis further revealed that Ndrg2 was located in different cellular fractions including the cytosol and cell surface membranes. These results suggest that Ndrg2 may regulate astroglial activation through the suppression of cell proliferation and stabilization of cell morphology. © 2011 Elsevier Ltd. All rights reserved

Effects of increased pCO2 and iron availability on phytoplankton assemblages in the Southern Ocean

第6回極域科学シンポジウム分野横断セッション：[IB1] 海氷域における生物地球化学的研究11月17日（火）　統計数理研究所 セミナー室1（D305

Ascorbic acid partly antagonizes resveratrol mediated heme oxygenase-1 but not paraoxonase-1 induction in cultured hepatocytes - role of the redox-regulated transcription factor Nrf2

<p>Abstract</p> <p>Background</p> <p>Both resveratrol and vitamin C (ascorbic acid) are frequently used in complementary and alternative medicine. However, little is known about the underlying mechanisms for potential health benefits of resveratrol and its interactions with ascorbic acid.</p> <p>Methods</p> <p>The antioxidant enzymes heme oxygenase-1 and paraoxonase-1 were analysed for their mRNA and protein levels in HUH7 liver cells treated with 10 and 25 μmol/l resveratrol in the absence and presence of 100 and 1000 μmol/l ascorbic acid. Additionally the transactivation of the transcription factor Nrf2 and paraoxonase-1 were determined by reporter gene assays.</p> <p>Results</p> <p>Here, we demonstrate that resveratrol induces the antioxidant enzymes heme oxygenase-1 and paraoxonase-1 in cultured hepatocytes. Heme oxygenase-1 induction by resveratrol was accompanied by an increase in Nrf2 transactivation. Resveratrol mediated Nrf2 transactivation as well as heme oxygenase-1 induction were partly antagonized by 1000 μmol/l ascorbic acid.</p> <p>Conclusions</p> <p>Unlike heme oxygenase-1 (which is highly regulated by Nrf2) paraoxonase-1 (which exhibits fewer ARE/Nrf2 binding sites in its promoter) induction by resveratrol was not counteracted by ascorbic acid. Addition of resveratrol to the cell culture medium produced relatively low levels of hydrogen peroxide which may be a positive hormetic redox-signal for Nrf2 dependent gene expression thereby driving heme oxygenase-1 induction. However, high concentrations of ascorbic acid manifold increased hydrogen peroxide production in the cell culture medium which may be a stress signal thereby disrupting the Nrf2 signalling pathway.</p

Impact estimation of Southern Ocean acidification on calcium carbonate phytoplankton (haptophytes)

第3回極域科学シンポジウム　横断セッション「南極海季節的海氷域における生物地球化学」11月26日（月） 統計数理研究所 セミナー