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Biomedical subjects

Go Nishimura

Publications and source records attributed to Go Nishimura.

7 recordsLinked to original sources
PubMed2006

A triethylenetetramine bearing anthracene and benzophenone as a fluorescent molecular logic gate with either-or switchable dual logic functions.

Fluorescence behaviors of a triethylenetetramine bearing anthracene (AN) and benzophenone (BP) fragments at the respective ends, L1, have been studied in water, where effects of pH (H+) and metal cations on the emission properties have been studied in detail. L1 behaves as a fluorescent molecular logic gate driven by H+ (Input1) and metal cations (Input2) as input chemicals. The most notable feature of L1 is that this molecule expresses the "either-or" switchable dual logic functions. Operation of L1 with Cu2+ as Input2 expresses the INHIBIT logic function, where a strong AN fluorescence appears only at pH 4 (with H+) without Cu2+ [Input1(1)-Input2(0)]. In contrast, operations of L1 with all other metal cations as Input2 express the TRANSFER logic function, where the presence of H+ allows strong AN fluorescence regardless of whether the metal cation exists or not [Input1(1)-Input2(0); Input1(1)-Input2(1)]. These emission switching behaviors of L1 are driven by the difference in the coordination stability between L1 and metal cations and the photoinduced intramolecular electron and energy transfer processes: (i) a pH-induced electron transfer from unprotonated nitrogen atoms of the polyamine chain to the photoexcited AN [ELT(N-->AN*)]; (ii) a pH- and metal coordination-induced electron transfer from the photoexcited AN to the ground-state BP [ELT(AN*-->BP)]; and (iii) a Cu2+ coordination-induced energy transfer from the photoexcited AN to Cu2+ [ENT(AN*-->Cu2+)].

Journal Article↗
PubMed2006

DeltaEF1 mediates TGF-beta signaling in vascular smooth muscle cell differentiation.

Alteration in the differentiated state of smooth muscle cells (SMCs) is known to be integral to vascular development and the pathogenesis of vascular disease. However, it is still largely unknown how environmental cues translate into transcriptional control of SMC genes. We found that deltaEF1 is upregulated during SMC differentiation and selectively transactivates the promoters of SMC differentiation marker genes, SM alpha-actin and SM myosin heavy chain (SM-MHC). DeltaEF1 physically interacts with SRF and Smad3, resulting in a synergistic activation of SM alpha-actin promoter. Chromatin immunoprecipitation assays and knockdown experiments showed that deltaEF1 is involved in the control of the SMC differentiation programs induced by TGF-beta signaling. Overexpression of deltaEF1 inhibited neointima formation and promoted SMC differentiation, whereas heterozygous deltaEF1 knockout mice exhibited exaggerated neointima formation. It thus appears deltaEF1 mediates SMC differentiation via interaction with SRF and Smad3 during development and in vascular disease.

Actins↗
PubMed2005

Synthetic retinoid Am80 suppresses smooth muscle phenotypic modulation and in-stent neointima formation by inhibiting KLF5.

Modulation of smooth muscle cell (SMC) phenotype plays a central role in neointima formation. We recently demonstrated that Am80, a synthetic retinoic acid receptor alpha-specific agonist, inhibits the activity of the transcription factor KLF5, which is essential for neointima formation after vascular injury. In the present study, we aimed to further analyze the mechanism by which Am80 inhibits KLF5 and the effects of inhibiting KLF5 on SMCs and vascular lesion formation, as well as to evaluate potential of Am80 for use in the prevention of in-stent neointima formation. We found that Am80 inhibited both the expression and transcriptional function of KLF5. Of particular interest was our finding that KLF5 forms a transcriptionally active complex with unliganded RAR/RXR heterodimer on the PDGF-A promoter; Am80 disrupts this complex, thereby inhibiting KLF5-dependent transcriptional activation. Knocking down KLF5 using small interfering RNA suppressed serum-induced downregulation of SMC differentiation marker gene expression in cultured SMCs, and haploinsufficiency of KLF5 in mice attenuated phenotypic modulation of SMCs after vascular injury, indicating that KLF5 plays a key role in the control of SMC phenotype. Am80 augmented expression of the SMC differentiation marker genes in culture and within the vessel walls, and oral administration of Am80 significantly inhibited in-stent neointima formation in a rabbit stent-placement model. Taken together, these results demonstrate that KLF5 plays an important role in the control of SMC phenotype after vascular injury and suggest the feasibility of using Am80, delivered systemically and/or with a drug eluting stent, to prevent in-stent neointima formation.

Actins↗
PubMed2005

Krüppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation.

Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor known to play a pivotal role in the pathogenesis of cardiovascular disease. Here, we show that neonatal heterozygous KLF5 knockout mice exhibit a marked deficiency in white adipose tissue development, suggesting that KLF5 is also required for adipogenesis. In 3T3-L1 preadipocytes, KLF5 expression was induced at an early stage of differentiation, and this was followed by expression of PPARgamma2. Constitutive overexpression of dominant-negative KLF5 inhibited adipocyte differentiation, whereas overexpression of wild-type KLF5 induced differentiation even without hormonal stimulation. Moreover, embryonic fibroblasts obtained from KLF5+/- mice showed much attenuated adipocyte differentiation, confirming the key role played by KLF5 in adipocyte differentiation. KLF5 expression is induced by C/EBPbeta and delta. KLF5, in turn, acts in concert with C/EBPbeta/delta to activate the PPARgamma2 promoter. This study establishes KLF5 as a key component of the transcription factor network controlling adipocyte differentiation.

3T3-L1 Cells↗
PubMed2003

A common Ile 823 Met variant of ATP-binding cassette transporter A1 gene (ABCA1) alters high density lipoprotein cholesterol level in Japanese population.

Recently, variants in ATP-binding cassette transporter A1 (ABCA1) were demonstrated to be associated with increased level of high density lipoprotein cholesterol (HDL-C) and decreased risk of coronary artery disease (CAD) in Caucasians. However, this is not universally applicable due to the ethnic or environmental differences. In this context, to clarify the effect of ABCA1 in Japanese, we evaluated the phenotypic effects of I/M 823 and R/K 219 variants on the plasma level of HDL-C in 410 patients recruited in our hospital. Subjects with M 823 allele had significantly higher level of HDL-C than those without M823 allele (49.0+/-15.1 vs. 44.9+/-11.5 mg/dl, respectively, P<0.05). This statistical significance did not change even after multiple regression analysis. In contrast, there was no difference in HDL-C level among the genotypes in R/K 219 polymorphism. Further, in our study population an inverse relationship was shown to exist between HDL-C level and incidence of CAD. However, no positive association was observed between those variants and susceptibility to CAD. In this study, we provide evidence that I/M 823 variant, not R/K 219 variant, in ABCA1 is one of the determinants of HDL-C level, suggesting the importance of this gene on lipid metabolism in Japanese.

ATP Binding Cassette Transporter 1↗