研究者詳細 - 宮﨑　育子

Effects of Bupropion and Pramipexole on Cell Proliferation in the Hippocampus of Adrenocorticotropic Hormone-Treated Rats 査読

Yuka Onoue, Keiko Kuwatsuka, Ikuko Miyazaki, Masato Asanuma, Yoshihisa Kitamura, Toshiaki Sendo

BIOLOGICAL & PHARMACEUTICAL BULLETIN 37 ( 2 ) 327 - 330 2014年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PHARMACEUTICAL SOC JAPAN

The dopamine reuptake inhibitor bupropion and dopamine D2/3 receptor agonist pramipexole have been clinically proven to improve both depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of the dopamine nerve system in this effect. Bupropion and pramipexole significantly decreased the duration of immobility in normal and ACTH-treated rats. We previously demonstrated that the chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation and neurogenesis. In this study, we used the mitotic marker 5-bromo-2'-deoxyridine to investigate the effects of bupropion and pramipexole on cell proliferation in the subgranular zone of the hippocampal dentate gyms following chronic treatment with ACTH. The ACTH treatment for 14 d decreased adult hippocampal cell proliferation. The chronic administration of bupropion for 14 d blocked the loss of cell proliferation resulting from the chronic treatment with ACTH, whereas pramipexole did not. The administration of bupropion may have treatment-resistant antidepressive properties, which may be partly attributed to the normalization of hippocampal cell proliferation.

DOI： 10.1248/bpb.b13-00749

Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice 査読

Hiromi Tachibana, Daisuke Ogawa, Norio Sogawa, Masato Asanuma, Ikuko Miyazaki, Naoto Terami, Takashi Hatanaka, Chikage Sato Horiguchi, Atsuko Nakatsuka, Jun Eguchi, Jun Wada, Hiroshi Yamada, Kohji Takei, Hirofumi Makino

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 306 ( 1 ) F105 - F115 2014年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER PHYSIOLOGICAL SOC

Oxidative stress and inflammation play important roles in diabetic complications, including diabetic nephropathy. Metallothionein (MT) is induced in proximal tubular epithelial cells as an antioxidant in the diabetic kidney; however, the role of MT in renal function remains unclear. We therefore investigated whether MT deficiency accelerates diabetic nephropathy through oxidative stress and inflammation. Diabetes was induced by streptozotocin injection in MT-deficient (MT-/-) and MT+/+ mice. Urinary albumin excretion, histological changes, markers for reactive oxygen species (ROS), and kidney inflammation were measured. Murine proximal tubular epithelial (mProx24) cells were used to further elucidate the role of MT under high-glucose conditions. Parameters of diabetic nephropathy and markers of ROS and inflammation were accelerated in diabetic MT-/- mice compared with diabetic MT+/+ mice, despite equivalent levels of hyperglycemia. MT deficiency accelerated interstitial fibrosis and macrophage infiltration into the interstitium in the diabetic kidney. Electron microscopy revealed abnormal mitochondrial morphology in proximal tubular epithelial cells in diabetic MT-/- mice. In vitro studies demonstrated that knockdown of MT by small interfering RNA enhanced mitochondrial ROS generation and inflammation-related gene expression in mProx24 cells cultured under high-glucose conditions. The results of this study suggest that MT may play a key role in protecting the kidney against high glucose-induced ROS and subsequent inflammation in diabetic nephropathy.

DOI： 10.1152/ajprenal.00034.2013

Transplantation of Melanocytes Obtained from the Skin Ameliorates Apomorphine-Induced Abnormal Behavior in Rodent Hemi-Parkinsonian Models 査読

Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Youichirou Higashi, Masayoshi Namba, Norio Ogawa

PLoS ONE 8 ( 6 ) e65983 2013年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-parkinsonian model rats or mice lesioned with 6-hydroxydopamine. Marked improvement in apomorphine-induced rotation was noted at day 40 after intrastriatal melanoma cell transplantation. Transplantation of tyrosinase cDNA-transfected hepatoma cells, which constitutively produce L-DOPA, resulted in marked amelioration of the asymmetric apomorphine-induced rotation in hemi-parkinsonian mice and the effect was present up to 2 months. Moreover, parkinsonian mice transplanted with melanocytes from the back skin of black newborn mice, but not from albino mice, showed marked improvement in the apomorphine-induced rotation behavior up to 3 months after the transplantation. Dopamine-positive signals were seen around the surviving transplants in these experiments. Taken together with previous studies showing dopamine synthesis and metabolism by tyrosinase, these results highlight therapeutic potential of intrastriatal autograft cell transplantation of melanocytes in patients with Parkinson's disease. © 2013 Asanuma et al.

DOI： 10.1371/journal.pone.0065983

Scopus

Protective effect of cepharanthin on cisplatin-induced renal toxicity through metallothionein expression 査読

Norio Sogawa, Kanji Hirai, Chiharu Sogawa, Kazumi Ohyama, Ikuko Miyazaki, Goichi Tsukamoto, Masato Asanuma, Akira Sasaki, Shigeo Kitayama

Life Sciences 92 ( 12 ) 727 - 732 2013年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Aims Cisplatin (CDDP) is a potent anticancer agent, but severe renal toxicity can limit its use. We investigated the protective effect of cepharanthin (CE), a biscoclaurin alkaloid, on the renal toxicity of CDDP. Main methods Mice were given CDDP along with CE. Effects of CE on CDDP toxicity were investigated by assaying markers of renal toxicity together with MT expression, and by histopathological examination of the kidney. MT-null mice were also examined. Key findings CE induced expression of metallothionein (MT). Pre-administration of CE attenuated an increase in blood urea nitrogen (BUN) concentrations after the CDDP injection. A histochemical analysis demonstrated protection against CDDP-induced necrocytosis of kidney tissues by CE. The protective effect of CE did not occur in the MT-null mice. Significance Pretreatment with CE may reduce the renal toxicity of CDDP through expression of MT. © 2013 Elsevier Inc.

DOI： 10.1016/j.lfs.2013.01.031

Scopus

アストロサイトとParkinson病治療

浅沼幹人, 宮崎育子

神経内科 79 ( 2 ) 262 - 268 2013年

培養アストログリア細胞における細胞保護効果．

喜多大三, 浅沼幹人, 宮崎育子, 竹島美香

九州栄養福祉大学研究紀要 ( 10 ) 179 - 191 2013年

The mechanisms of electroconvulsive stimuli in BrdU-positive cells of the dentate gyrus in ACTH-treated rats 査読

Keiko Kuwatsuka, Hiromi Hayashi, Yuka Onoue, Ikuko Miyazaki, Toshihiro Koyama, Masato Asanuma, Yoshihisa Kitamura, Toshiaki Sendo

Journal of Pharmacological Sciences 122 ( 1 ) 34 - 41 2013年

記述言語：英語掲載種別：研究論文（学術雑誌）

In clinical studies, electroconvulsive stimuli have been associated with improvements in both depression and treatment-resistant depression. In a previous study, treatment with adrenocorticotropic hormone (ACTH) for 14 days decreased adult hippocampal cell proliferation. Furthermore, electroconvulsive stimuli significantly decreased the duration of immobility following repeated administration of ACTH for 14 days in rats. The present study was undertaken to further characterize the mechanism of treatment-resistant antidepressant effects of electroconvulsive stimuli by measuring cell proliferation, brain-derived neurotrophic factor (BDNF) levels, and phosphorylated and total cyclic adenosine monophosphate (cAMP) response element-binding protein (pCREB/CREB) levels in the hippocampus of ACTH-treated rats. Electroconvulsive stimuli increased cell proliferation in both saline-treated and ACTH-treated rats. Mature-BDNF protein levels showed a tendency to decrease in ACTH-treated rats. Electroconvulsive stimuli treatment increased mature-BDNF protein levels in the hippocampus of both saline-treated and ACTH-treated rats. Furthermore, electroconvulsive stimuli increased phospho-Ser133-CREB (pCREB) levels and the ratio of pCREB/CREB in both saline-treated and ACTH-treated rats. These findings suggest that the treatment-resistant antidepressant effects of electroconvulsive stimuli may be attributed, at least in part, to an enhancement of hippocampal cell proliferation. © The Japanese Pharmacological Society.

DOI： 10.1254/jphs.13015FP

Scopus

Centrosomal aggregates and Golgi fragmentation disrupt vesicular trafficking of DAT 査読

Francisco J. Diaz-Corrales, Ikuko Miyazaki, Masato Asanuma, Diego Ruano, Rosa M. Rios

Neurobiology of Aging 33 ( 10 ) 2462 - 2477 2012年10月

Cyclooxygenase-Independent Neuroprotective Effects of Aspirin Against Dopamine Quinone-Induced Neurotoxicity 査読

Masato Asanuma, Ikuko Miyazaki, Yuri Kikkawa, Naotaka Kimoto, Mika Takeshima, Shinki Murakami, Ko Miyoshi

NEUROCHEMICAL RESEARCH 37 ( 9 ) 1944 - 1951 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER/PLENUM PUBLISHERS

Prostaglandin H synthase exerts not only cyclooxygenase activity but also peroxidase activity. The latter activity of the enzyme is thought to couple with oxidation of dopamine to dopamine quinone. Therefore, it has been proposed that cyclooxygenase inhibitors could suppress dopamine quinone formation. In the present study, we examined effects of various cyclooxygenase inhibitors against excess methyl L-3,4-dihydroxyphenylalanine (L-DOPA)-induced quinoprotein (protein-bound quinone) formation and neurotoxicity using dopaminergic CATH.a cells. The treatment with aspirin inhibited excess methyl L-DOPA-induced quinoprotein formation and cell death. However, acetaminophen did not show protective effects, and indomethacin and meloxicam rather aggravated these methyl L-DOPA-induced changes. Aspirin and indomethacin did not affect the level of glutathione that exerts quenching dopamine quinone in dopaminergic cells. In contrast with inhibiting effects of higher dose in the previous reports, relatively lower dose of aspirin that affected methyl L-DOPA-induced quinoprotein formation and cell death failed to prevent cyclooxygenase-induced dopamine chrome generation in cell-free system. Furthermore, aspirin but not acetaminophen or meloxicam showed direct dopamine quinone-scavenging effects in dopamine-semiquinone generating systems. The present results suggest that cyclooxygenase shows little contribution to dopamine oxidation in dopaminergic cells and that protective effects of aspirin against methyl L-DOPA-induced dopamine quinone neurotoxicity are based on its cyclooxygenase-independent property.

DOI： 10.1007/s11064-012-0813-2

EFFLUENT FREE RADICALS ARE ASSOCIATED WITH RESIDUAL RENAL FUNCTION AND PREDICT TECHNIQUE FAILURE IN PERITONEAL DIALYSIS PATIENTS 査読

Hiroshi Morinaga, Hitoshi Sugiyama, Tatsuyuki Inoue, Keiichi Takiue, Yoko Kikumoto, Masashi Kitagawa, Shigeru Akagi, Kazushi Nakao, Yohei Maeshima, Ikuko Miyazaki, Masato Asanuma, Makoto Hiramatsu, Hirofumi Makino

PERITONEAL DIALYSIS INTERNATIONAL 32 ( 4 ) 453 - 461 2012年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MULTIMED INC

Objective: Residual renal function (RRF) is associated with low oxidative stress in peritoneal dialysis (PD). In the present study, we investigated the relationship between the impact of oxidative stress on RRF and patient outcomes during PD.
Methods: Levels of free radicals (FRs) in effluent from the overnight dwell in 45 outpatients were determined by electron spin resonance spectrometry. The FR levels, clinical parameters, and the level of 8-hydroxy-2'-deoxyguanosine were evaluated at study start. The effects of effluent FR level on technique and patient survival were analyzed in a prospective cohort followed for 24 months.
Results: Levels of effluent FRs showed significant negative correlations with daily urine volume and residual renal Kt/V, and positive correlations with plasma beta(2)-microglobulin and effluent 8-hydroxy-2'-deoxyguanosine. A highly significant difference in technique survival (p < 0.05), but not patient survival, was observed for patients grouped by effluent FR quartile. The effluent FR level was independently associated with technique failure after adjusting for patient age, history of cardiovascular disease, and presence of diabetes mellitus (p < 0.001). The level of effluent FRs was associated with death-censored technique failure in both univariate (p < 0.001) and multivariate (p < 0.01) hazard models. Compared with patients remaining on PD, those withdrawn from the modality had significantly higher levels of effluent FRs (p < 0.005).
Conclusions: Elevated effluent FRs are associated with RRF and technique failure in stable PD patients. These findings highlight the importance of oxidative stress as an unfavorable prognostic factor in PD and emphasize that steps should be taken to minimize oxidative stress in these patients. Perit Dial Int 2012; 32(4): 453-461

DOI： 10.3747/pdi.2011.00032

ACTH反復投与ラットにおける海馬細胞新生の減少及びそのメカニズムに関する検討．

林宏美, 土居真穂, 尾上由華, 鍬塚圭子, 三宅彩香, 小山敏広, 四宮一昭, 宮崎育子, 浅沼幹人, 北村佳久

薬学雑誌 173 - 178 2012年

テアニンの中枢作用に関する文献的考察．

喜多大三, 浅沼幹人, 宮崎育子, 竹島美香

九州栄養福祉大学研究紀要 ( 9 ) 45 - 58 2012年

Protective effects of baicalein against excess L-DOPA-induced dopamine quinone neurotoxicity 査読

Mika Takeshima, Maiko Murata, Natsuho Urasoe, Shinki Murakami, Ikuko Miyazaki, Masato Asanuma, Taizo Kita

NEUROLOGICAL RESEARCH 33 ( 10 ) 1050 - 1056 2011年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MANEY PUBLISHING

Objectives: Baicalein, a flavonoid derived from the root of Scutelaria baicalensis Georgi, possesses antioxidative properties including reactive oxygen species scavenging and lipid peroxidation inhibiting activities. The present study was undertaken to investigate the neuroprotective effect of baicalein against dopamine (DA) neurotoxicity induced by exposure to a synthetic DA precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), in cultured dopaminergic CATH. a cells.
Methods and results: Exposure to L-DOPA for 24 hours reduced the number of viable cells and enhanced protein-bound quinone (quinoprotein) formation in the cell. Both effects were prevented by simultaneous treatment with baicalein. In addition, baicalein prevented the formation of DA semiquinone radicals from DA in an in vitro cell-free system. Long-term baicalein treatment for 96 hours also protected against excess L-DOPA-induced cell death, and also increased glutathione (GSH) levels in CATH. a cells.
Discussion: Our results indicate that baicalein has neuroprotective properties against excess L-DOPA-induced DA neurotoxicity through the suppression of DA quinone formation. Furthermore, the long-term treatment of baicalein upregulates intracellular GSH contents, which may also exert neuroprotective effects against oxidative stress-induced neuronal damage.

DOI： 10.1179/1743132811Y.0000000032

Factors That Influence Primary Cilium Length 査読

Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Masato Asanuma

ACTA MEDICA OKAYAMA 65 ( 5 ) 279 - 285 2011年10月

記述言語：英語出版者・発行元：OKAYAMA UNIV MED SCHOOL

Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells; this phenomenon is likely independent of glycogen synthase kinase-3 beta inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the cytosol available for primary cilia extension. Thus, mammalian cells can adapt to the extracellular environment by modulating the primary cilium length, and this feedback system utilizing primary cilia might exist throughout the mammalian body. Further investigation is required concerning the precise molecular mechanisms underlying the control of primary cilium length in response to environmental factors.

DOI： 10.18926/AMO/47009

A Novel Hypothesized Clinical Implication of Zonisamide for Autism Reply

Masato Asanuma, Ikuko Miyazaki

ANNALS OF NEUROLOGY 69 ( 2 ) 426 - 427 2011年2月

Chronic Treatment with Imipramine and Lithium Increases Cell Proliferation in the Hippocampus in Adrenocorticotropic Hormone-Treated Rats 査読

Yoshihisa Kitamura, Maho Doi, Keiko Kuwatsuka, Yuka Onoue, Ikuko Miyazaki, Kazuaki Shinomiya, Toshihiro Koyama, Toshiaki Sendo, Hiromu Kawasaki, Masato Asanuma, Yutaka Gomita

BIOLOGICAL & PHARMACEUTICAL BULLETIN 34 ( 1 ) 77 - 81 2011年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PHARMACEUTICAL SOC JAPAN

Adult hippocampal neurogenesis is reported to change in animal models of depression and antidepressants. We have used the mitotic marker 5-bromo-2'-deoxyyridine to address the effects of imipramine and lithium on cell proliferation and survival following chronic treatment with adrenocorticotropic hormone (ACTH) in the subgranular zone of the hippocampal dentate gyrus. ACTH treatment for 14d decreased adult hippocampal cell proliferation and survival. Coadministration of imipramine and lithium for 14d blocked the loss of cell proliferation but not cell survival resulting from the chronic treatment with ACTH. The coadministration of imipramine and lithium may have treatment-resistant antidepressive properties, which may be attributed, in part, to a normalization of hippocampal cell proliferation.

DOI： 10.1248/bpb.34.77

L-テアニンのグリア細胞に対する保護作用に関する研究─アストロサイトにおけるL-テアニンによる抗酸化保護作用の賦活─

パーキンソン病とアストロサイト─新たな神経保護療法の標的

浅沼幹人, 宮崎育子

Clinical Neuroscience 29 1295 - 1297 2011年

喜多大三, 浅沼幹人, 宮崎育子, 竹島美香

九州栄養福祉大学研究紀要 8 ( 8 ) 43 - 53 2011年

High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells 査読国際誌

Daisuke Ogawa, Masato Asanuma, Ikuko Miyazaki, Hiromi Tachibana, Jun Wada, Norio Sogawa, Takeshi Sugaya, Shinji Kitamura, Yohei Maeshima, Kenichi Shikata, Hirofumi Makino

Experimental Diabetes Research 2011 1 - 8 2011年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Hindawi Limited

Metallothionein (MT) is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2) are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.

DOI： 10.1155/2011/534872