Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions.
Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions.
复制标题
DOI：
10.3390/ijms22179493
复制
发表时间：
2021-08-31
影响因子：
5.6
通讯作者：
Borutaite V
中科院分区：
文献类型：
--
作者：
Jankeviciute S;Svirskiene N;Svirskis G;Borutaite V
小胶质细胞的功能依赖于Ca 2+信号。利用钙敏感的荧光染料，我们研究了在常氧和轻度缺氧条件下生长的5-7日龄大鼠的小胶质细胞索马中，线粒体呼吸抑制如何改变自发性钙信号。在常氧条件下的小胶质细胞中，二甲双胍或鱼藤酮在给药后10-15分钟提高了Ca 2+信号的速率和振幅。在鱼藤酮存在下，加入环孢菌素A、线粒体通透性转换孔（mPTP）阻断剂、抗氧化剂trolox或肌醇1，4，5-三磷酸受体（IP 3R）阻断剂咖啡因降低了信号的升高速率和幅度，这意味着对活性氧（ROS）的敏感性，以及线粒体mPTP与IP 3R的参与。轻度缺氧24 h后，小胶质细胞Ca 2+信号的频率和幅度均升高。在轻度缺氧前应用二甲双胍或鱼藤酮而非苯丙氨酸可降低这种升高的速率。因此，二甲双胍和鱼藤酮在常氧10-15分钟后具有相反的快速作用，而在24小时轻度缺氧期间具有缓慢作用，这意味着不同的信号通路的激活。二甲双胍通过抑制复合物I的缓慢作用可以稳定轻度缺氧后的Ca 2+稳态，并且对于减少缺血诱导的小胶质细胞活化可能是重要的。
Microglial functioning depends on Ca2+ signaling. By using Ca2+ sensitive fluorescence dye, we studied how inhibition of mitochondrial respiration changed spontaneous Ca2+ signals in soma of microglial cells from 5–7-day-old rats grown under normoxic and mild-hypoxic conditions. In microglia under normoxic conditions, metformin or rotenone elevated the rate and the amplitude of Ca2+ signals 10–15 min after drug application. Addition of cyclosporin A, a blocker of mitochondrial permeability transition pore (mPTP), antioxidant trolox, or inositol 1,4,5-trisphosphate receptor (IP3R) blocker caffeine in the presence of rotenone reduced the elevated rate and the amplitude of the signals implying sensitivity to reactive oxygen species (ROS), and involvement of mitochondrial mPTP together with IP3R. Microglial cells exposed to mild hypoxic conditions for 24 h showed elevated rate and increased amplitude of Ca2+ signals. Application of metformin or rotenone but not phenformin before mild hypoxia reduced this elevated rate. Thus, metformin and rotenone had the opposing fast action in normoxia after 10–15 min and the slow action during 24 h mild-hypoxia implying activation of different signaling pathways. The slow action of metformin through inhibition of complex I could stabilize Ca2+ homeostasis after mild hypoxia and could be important for reduction of ischemia-induced microglial activation.
登录
查看更多内容
影响因子：
--
作者：
Fang M;Jiang H;Ye L;Cai C;Hu Y;Pan S;Li P;Xiao J;Lin Z
通讯作者：
Lin Z
影响因子：
3.9
作者：
Cizas, Paulius;Budvytyte, Rima;Morkuniene, Ramune;Moldovan, Radu;Broccio, Matteo;Loesche, Mathias;Niaura, Gediminas;Valincius, Gintaras;Borutaite, Vilmante
通讯作者：
Borutaite, Vilmante
影响因子：
11.4
作者：
Chowdhury, Anindya Roy;Zielonka, Jacek;Avadhani, Narayan G.
通讯作者：
Avadhani, Narayan G.
影响因子：
11.4
作者：
Cameron AR;Logie L;Patel K;Erhardt S;Bacon S;Middleton P;Harthill J;Forteath C;Coats JT;Kerr C;Curry H;Stewart D;Sakamoto K;Repiščák P;Paterson MJ;Hassinen I;McDougall G;Rena G
通讯作者：
Rena G
影响因子：
16.2
作者：
Agarwal A;Wu PH;Hughes EG;Fukaya M;Tischfield MA;Langseth AJ;Wirtz D;Bergles DE
通讯作者：
Bergles DE