Yasutomo Fukunaga

Publications (24)91.37 Total impact

• Article: HYPERTENSION AND INSULIN RESISTANCE: ROLE OF PEROXISOME PROLIFERATOR‐ACTIVATED RECEPTOR γ

  Hiroshi Itoh, Kentaro Doi, Tokuji Tanaka, Yasutomo Fukunaga, Kiminori Hosoda, Gen Inoue, Haruhiko Nishimura, Yasunao Yoshimasa, Yukio Yamori, Kazuwa Nakao
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  ABSTRACT: 1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as ‘multiple risk factor syndrome’.2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR)γ.3. cDNA of rat PPARγ1 and γ2 were cloned and gene regulation of PPARγ in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPARγ mRNA expression in rat mature adipocytes.4. Tumour necrosis factor (TNF)-α, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPARγ expression.5. Thiazolidinediones dose-dependently recovered TNF-α-induced down-regulation of PPARγ mRNA expression.6. The modulation of PPARγ expression by TZD can be one mechanism for the improvement of insulin resistance by TZD.7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPARγ gene transcript was detected in cultured endothelial cells.8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide.9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide.10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.
  Clinical and Experimental Pharmacology and Physiology 02/2002; 26(7):558 - 560. · 1.85 Impact Factor
• Article: cGMP-Dependent Protein Kinase Phosphorylates and Inactivates RhoA

  Naoki Sawada, Hiroshi Itoh, Jun Yamashita, Kentaro Doi, Mayumi Inoue, Ken Masatsugu, Yasutomo Fukunaga, Satsuki Sakaguchi, Masakatsu Sone, Ken-ichi Yamahara, Takami Yurugi, Kazuwa Nakao
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  ABSTRACT: Small GTPase Rho and cGMP/cGMP-dependent protein kinase (cGK) pathways exert opposing effects in specific systems such as vascular contraction and growth. However, the direct interaction between these pathways has remained elusive. We demonstrate that cGK phosphorylates RhoA in vitro at Ser188, the same residue phosphorylated by cAMP-dependent protein kinase. In HeLa cells transfected with constitutively active cGK (C-cGK), stress fiber formation induced by lysophosphatidic acid or V14RhoA was blocked. By contrast, C-cGK failed to inhibit stress fiber formation in cells transfected with mutant RhoA with substitution of Ser188 to Ala. C-cGK did not affect actin reorganization induced by Rac1 or Rho-associated kinase, one of the effectors for RhoA. Furthermore, C-cGK expression inhibited the membrane translocation of RhoA. Collectively, our findings suggest that cGK phosphorylates RhoA at Ser188 and inactivates RhoA signaling. The physiological relevance of the direct interaction between RhoA and cGK awaits further investigation.
  Biochemical and Biophysical Research Communications 02/2001; · 2.48 Impact Factor
• Article: Correction: Augmentation of Neovascularization in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells

  Kenichi Yamahara, Masakatsu Sone, Hiroshi Itoh, Jun K Yamashita, Takami Yurugi-Kobayashi, Koichiro Homma, Ting-Hsing Chao, Kazutoshi Miyashita, Kwijun Park, Naofumi Oyamada, Naoya Sawada, Daisuke Taura, Yasutomo Fukunaga, Naohisa Tamura, Kazuwa Nakao
• Article: Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs: their gene expression in rats fed high-fat diet

  Junichi Matsuda, Kiminori Hosoda, Hiroshi Itoh, Cheol Son, Kentaro Doi, Tokuji Tanaka, Yasutomo Fukunaga, Gen Inoue, Haruo Nishimura, Yasunao Yoshimasa, Yukio Yamori, Kazuwa Nakao
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  ABSTRACT: In order to elucidate energy balance in the skeletal muscle, we cloned cDNA of a homologue of uncoupling protein (UCP) from rat skeletal muscle. We also cloned rat UCP-2 cDNA from rat brown adipose tissue (BAT). The UCP cloned from rat skeletal muscle showed 57% and 72% identity with rat UCP-1 and UCP-2. The mRNA was expressed abundantly in the skeletal muscle, moderately in the BAT, and slightly in the white adipose tissue (WAT) with a major band at 2.5 kb and a minor band at 2.8 kb, while the UCP-2 gene expression was widely detected in the whole body with substantial levels in the WAT and with slight levels in the skeletal muscle and BAT. The rat UCP cloned in the present study showed 86% identity with the recently cloned human UCP-3, which was also expressed abundantly in the skeletal muscle with a signal of 2.4 kb. Therefore, the rat UCP was considered to be rat UCP-3. In rats fed high-fat diet the UCP-3 gene expression was augmented 2-fold in the skeletal muscle while UCP-2 mRNA levels were increased significantly (1.6-fold) in the epididymal WAT. Augmented expression of UCPs may provide defense against high-fat induced obesity and impairment of glucose metabolism.
  FEBS Letters.