Showing papers by "Atsushi Enomoto published in 2010"

Indoxyl sulfate upregulates expression of ICAM-1 and MCP-1 by oxidative stress-induced NF-kappaB activation.

Abstract: Background/Aim: Indoxyl sulfate, a uremic toxin, is considered a risk factor for cardiovascular disease (CVD) in chronic kidney disease (CKD). The present study aimed to determine w

Senescence and dysfunction of proximal tubular cells are associated with activated p53 expression by indoxyl sulfate

Abstract: Various uremic toxins accumulate in patients with chronic renal failure (CRF) and one of them is indoxyl sulfate, which accelerates the progression of CRF through unknown mechanisms. The present st...

Girding for migratory cues: roles of the Akt substrate Girdin in cancer progression and angiogenesis.

Abstract: Cell migration is a fundamental aspect of a multitude of physiological and pathological processes, including embryonic development, inflammation, angiogenesis, and cancer progression. A variety of proteins are essential for cell migration, but context-specific signaling pathways and promigratory proteins must now be identified for our understanding of cancer biology to continue to advance. In this review, we focus on the emerging roles of Girdin (also designated KIAA1212, APE, GIV, and HkRP1), a novel component of the phosphatidylinositol 3-kinase (PI3-K) ⁄Akt signaling pathway that is a core-signaling transduction pathway in cancer progression. Girdin is expressed in some types of cancer cells and immature endothelial cells, and is therefore at the crossroads of multiple intracellular processes, including reorganization of the actin cytoskeleton, endocytosis, and modulation of Akt activity, which ultimately lead to cancer invasion and angiogenesis. It also acts as a nonreceptor guanine nucleotide exchange factor (GEF) for Gai proteins. A significant observation is that Girdin, although vital for cancer progression and postnatal vascular remodelling, is dispensable for cell migratory events during embryonic development. These findings suggest that Girdin and its interacting proteins are potential pharmaceutical targets for cancer therapies and pathological anigiogenesis, including tumor angiogenesis. (Cancer Sci 2010; 101: 836‐842)

Identification of a novel organic anion transporter mediating carnitine transport in mouse liver and kidney.

Abstract: This study identifies a novel organic anion transporter Oat9 expressed in mouse liver and kidney. Two variants were detected by screening a mouse liver cDNA library; these varients consist of 1815 (designated Oat9S) and 2165 (Oat9L) base pairs which encode 443 and 551 amino acid proteins, respectively. Oat9S has a predicted structure containing eight transmembrane domains (TMD); whereas, Oat9L possesses twelve TMD. Oat9 mRNA expression was detected in kidney and liver. This transporter was located at the apical side of the late portion of proximal tubules and at the sinusoidal side of hepatocytes. When expressed in Xenopus oocytes, Oat9S mediated the transport of L-carnitine (Km = 2.9 µM), a representative zwitterion, as well as cimetidine (Km = 16.1 µM) and salicylic acid (Km = 175.5 µM), while Oat9L did not show any transport activity. Oat9S-mediated L-carnitine uptake was inhibited by D-carnitine, acetylcarnitine, octanoylcarnitine, betaine, and other organic compounds, suggesting that quaternary ammonium cation bulkiness and relative hydrophobicity are important factors for Oat9S-substrate interactions. Among OATs, Oat9S appears to be the first member to mediate the transport of carnitine and possesses eight TMD. Overall, these new results provide added insight into the structure-activity relationship comprising the organic ion-permeation pathway.

Analysis of DOK‐6 function in downstream signaling of RET in human neuroblastoma cells

Abstract: Point mutations and structural alterations of the RET tyrosine kinase gene cause multiple endocrine neoplasia type 2 (MEN 2) and papillary thyroid carcinoma, respectively. RET activation by glial cell line-derived neurotrophic factor (GDNF) is essential for the development of the enteric nervous system and the kidney. The signal through RET tyrosine kinase requires several adaptor proteins including the DOK (downstream of kinase) family of proteins. Of the seven members of the DOK protein family, DOK-1, -4, -5, and -6 have been reported to play roles in the GDNF–RET signaling pathway. Although DOK-6 has been shown to bind to RET and promote GDNF-induced neurite outgrowth in mouse Neuro2A cells, DOK-6 function in human cells remains unclear. In the present study, we investigated the role of DOK-6 in GDNF–RET signaling in human cells including neuroblastoma cells. DOK-6 was constitutively localized to the plasma membrane via its pleckstrin homology (PH) domain, and was phosphorylated following RET activation via a MEN2A mutation or GDNF stimulation. However, DOK-6 could not significantly affect downstream signaling and neurite outgrowth in human neuroblastoma cells. The binding affinity of the DOK-6 phosphotyrosine-binding (PTB) domain to RET was much lower than that of the DOK-1, DOK-4, and SHC PTB domains to RET. These findings indicate that DOK-6 is involved in RET signaling with less influence when compared with DOK-1, DOK-4, and SHC. (Cancer Sci 2010; 101: 1047–1155)

Radiographic imaging device, radiographic imaging system, radiographic imaging program, and radiographic imaging method

Abstract: PROBLEM TO BE SOLVED: To provide a radiographic imaging device, a radiographic imaging system, a radiographic imaging program, and a radiographic imaging method that prevent the output of a false radiographic image that is not valid, from a radiographic imaging device that images a radiographic image.SOLUTION: The dose of irradiated radiation that has been irradiated from a radiation generation device 16 is detected when acquiring the offset image data, and it is determined that the imaged radiographic image is not the valid image when the detected dose of radiation is less than a threshold value or when the detected dose of radiation is equal to or greater than the threshold value and a period until the detected dose of radiation reaches the threshold value exceeds a predetermined period, the wireless communication section 40 is controlled not to output the radiographic image to the control device 12. When the detected dose of radiation is equal to or greater than the threshold value and when the period is equal to or less than the predetermined period, it is determined that the imaged radiographic is a valid image and instructs the wireless communication section 40 to output the radiographic image to the control device 12.