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学科主题: 基础医学
题名:
Potential regulatory role of calsequestrin in platelet Ca2+ homeostasis and its association with platelet hyperactivity in diabetes mellitus
作者: Zhu, Z.; Zhou, H.2; Yu, X.; Chen, L.; Zhang, H.3; Ren, S.; Wu, Y.3; Luo, D.1
关键词: aggregation ; Ca2+signaling ; calsequestrin ; diabetes ; platelets
刊名: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
发表日期: 2012
DOI: 10.1111/j.1538-7836.2011.04550.x
卷: 10, 期:1, 页:116-124
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Hematology ; Cardiovascular System & Cardiology
关键词[WOS]: SARCOPLASMIC-RETICULUM ; RELEASE CHANNEL ; MUSCLE ; CA2+-ATPASE ; CALCIUM ; STORE ; CELLS ; EXPRESSION ; MECHANISM ; SKELETAL
英文摘要:

Background: Altered Ca2+ homeostasis contributes significantly to platelet hyperactivity in diabetes mellitus. Calsequestrin (CSQ), as a Ca2+ buffer protein in the sarcoplasmic reticulum, also regulates the Ca2+ release process in muscles. We hypothesized that CSQ may be expressed in platelets, but is altered and involved in diabetic platelet Ca2+ abnormalities and hyperaggregability. Methods: CSQ expression in platelets from streptozotocin-induced type 1 diabetes rats, type 2 diabetes volunteers and Goto-Kakizaki rats were analyzed by western blotting and RT-qPCR. Platelet Ca2+ and aggregation were evaluated with Fura2 and an aggregometer, respectively. Results: Platelets from diabetic patients and rats exhibited increased resting Ca2+ levels, and hyperactive Ca2+ and aggregation responses to agonists. This enhanced basal Ca2+ was largely dependent on intracellular Ca2+ and insensitive to inositol 1,4,5-trisphosphate receptor (IP3R) antagonism. Additionally, the expression of the skeletal CSQ isotype (CSQ-1) was detected in both rat and human platelets, but its levels were significantly lowered in diabetic platelets as compared with normal platelets. Impairment of CSQ by trifluoperazine caused concentration-dependent Ca2+ release in normal platelets and HEK293 cells. Knocking down CSQ-1 in HEK293 cells resulted in increased leakage of Ca2+, which was also insensitive to IP3R inhibition, and exaggerated Ca2+ release following carbachol treatment. Conclusions: Downregulation of CSQ-1 in diabetic platelets and impairment of CSQ-1 in normal cells leads to disturbed Ca2+ release, demonstrating a potential role for CSQ-1 in the regulation of the platelet Ca2+ release process and a possible causal contribution to diabetic platelet hyperactivity.

语种: 英语
所属项目编号: 30973537 ; 30772574 ; 7082018
项目资助者: National Natural Science Foundation ; Beijing Natural Science Foundation
WOS记录号: WOS:000298843500015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53412
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Capital Med Univ, Dept Pharmacol, Sch Chem Biol & Pharmaceut Sci, Beijing 100069, Peoples R China
2.Peking Univ, Dept Pharmacol, Med Sci Ctr, Beijing 100871, Peoples R China
3.Capital Med Univ, Dept Cardiol, Beijing Friendship Hosp Aliated, Beijing 100069, Peoples R China

Recommended Citation:
Zhu, Z.,Zhou, H.,Yu, X.,et al. Potential regulatory role of calsequestrin in platelet Ca2+ homeostasis and its association with platelet hyperactivity in diabetes mellitus[J]. JOURNAL OF THROMBOSIS AND HAEMOSTASIS,2012,10(1):116-124.
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