IR@PKUHSC  > 北京大学基础医学院  > 药理学系
学科主题基础医学
Potential regulatory role of calsequestrin in platelet Ca2+ homeostasis and its association with platelet hyperactivity in diabetes mellitus
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
2012
DOI10.1111/j.1538-7836.2011.04550.x
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
WOS记录号WOS:000298843500015
项目编号30973537 ; 30772574 ; 7082018
资助机构National Natural Science Foundation ; Beijing Natural Science Foundation
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53412
专题北京大学基础医学院_药理学系
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
推荐引用方式
GB/T 7714
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.
APA Zhu, Z..,Zhou, H..,Yu, X..,Chen, L..,Zhang, H..,...&Luo, D..(2012).Potential regulatory role of calsequestrin in platelet Ca2+ homeostasis and its association with platelet hyperactivity in diabetes mellitus.JOURNAL OF THROMBOSIS AND HAEMOSTASIS,10(1),116-124.
MLA Zhu, Z.,et al."Potential regulatory role of calsequestrin in platelet Ca2+ homeostasis and its association with platelet hyperactivity in diabetes mellitus".JOURNAL OF THROMBOSIS AND HAEMOSTASIS 10.1(2012):116-124.
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