Project/Area Number |
17590482
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Laboratory medicine
|
Research Institution | Hirosaki University |
Principal Investigator |
SHOJI Masaru Hirosaki University, School of Medicine, Associate Professor, 医学部, 助教授 (10226300)
|
Co-Investigator(Kenkyū-buntansha) |
YASUJIMA Minoru Hirosaki University, School of Medicine, Professor, 医学部, 教授 (90142934)
SUGIMOTO Kazuhiro Hirosaki University, University Hospital, Lecturer, 医学部附属病院, 講師 (70271799)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | gene expression / microRNA / vasopressin / peripheral CD34(+) stem cell / microarray / mass spectrometry / 遺伝子 / シグナル伝達 / 生体分子 / バゾプレシンV1a受容体 |
Research Abstract |
There is a significant inter-individual divergence in the platelet aggregation response to arginine vasopressin (AVP). In the present study, high-throughput microarray analysis was conducted to explore molecules, which are responsible for the heterogeneity. Responders and non-responders were divided using platelet aggregation analyzer MCM hematracer 313 (Model PAM-12C). Hitachi Ace-Gene micro array analysis showed characteristic gene expression profiling. Namely, responder platelets had increased gene expressions of sodium channel, voltage-gated, type., alpha, mannose-P-dolichol utilization defect 1、eukaryotic translation termination factor 1、cysteine and glycine-rich protein 2、and general transcription factor IIH, polypeptide 2,44kDa. In non-responder platelets, genes including component of oligomeric golgi complex 6、Hermansky-Pudlak syndrome 3、PERM domain containing 1、adenosine monophosphate deaminase 2 (isoform L) nudix-type motif 1、and cell growth regulator with ring finger domain 1 were upregulated. Mass spectrometry analysis demonstrated increased platelet protein levels of protease serine 4 isoform B、and keratin 1b、trypsin family in responders and of TPMsk1、TPM3 protein、and YWHAZ protein in non-responders. There were also increased microRNA levels including hsa let 7d、hsa let 7e、hsa miR 198、hsa miR 99b、and hsa miR 98 in AVP stimulated peripheral CD34(+) stem cells (megakaryocyte progenitor cells). AVP Vla receptor gene polymorphism 242C/T showed an association with its gene expression. From these results, numbers of factors were likely to be responsible for the inter-individual heterogeneity in the platelet aggregation response to AVP.
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