Improvement of platelet preservation by inhibition of TRPC6

TRPC6型 化学 血小板 流式细胞术 磷脂酰丝氨酸 血小板活化 男科 生物物理学 分子生物学 生物化学 免疫学 受体 生物 医学 瞬时受体电位通道 磷脂
作者
Yuanjia Tan,Wei Lu,Xiaomei Yi,Huili Cai,Yurong Yuan,Shizhong Zhang
出处
期刊:Transfusion Medicine [Wiley]
卷期号:33 (3): 232-243 被引量:1
标识
DOI:10.1111/tme.12955
摘要

The preservation of platelets (PLTs) by room temperature (RT) oscillation limits their shelf life to between 4 and 7 days because of the decrease in PLT function. TRPC6 is a non-selective mechanically sensitive cation channel that has been shown to mediate Ca2+ signalling, implying a role in PLT activation during preservation by RT oscillation.This study was designed to investigate whether inhibition of TRPC6 can improve the RT preservation of PLTs and the possible underlying mechanism.Human PLTs from whole blood were stored at 22 ± 2°C with oscillation in plasma or M-sol (mixture of solutions). BI-749327, a specific TRPC6 inhibitor, was administered throughout the preservation period. PLT distribution width (PDW), mean platelet volume (MPV), maximum platelet aggregation rate (MAR) and average aggregation rate (AAR) were measured. The MTT method was used to assess the relative viability of PLTs. Flow cytometry was used to measure the changes of Ca2+ concentration in PLTs and phosphatidylserine (PS) exposure on the PLT surface, and western blotting was used to assess the expression changes of platelet TRPC6 and CD62P proteins.Compared with the control group, inhibition of TRPC6 with BI-749327 significantly reduced the PDW, MPV and Ca2+ concentration, the MAR and AAR were significantly increased, the expression of TRPC6 and CD62P protein was significantly down-regulated in PLTs, and the PS exposure was significantly reduced on the PLT surface. However, these effects were all reversed by activation of TRPC6.Inhibition of TRPC6 improves the quality of PLT preservation by inhibiting the Ca2+ signal mediated by TRPC6.
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