TY - JOUR
T1 - Cholesterol-induced robust Ca oscillation in astrocytes required for survival and lipid droplet formation in high-cholesterol condition
AU - Adachi, Chihiro
AU - Otsuka, Shio
AU - Inoue, Takafumi
N1 - Funding Information:
We thank Drs. K. F. Tanaka and A. Natsubori for providing Mlc1-YC Nano50 mice, and Dr. A. Miyawaki for providing plasmid encoding YC3.60. This work was supported by Waseda University Grants for Special Research Projects (C.A.: 2020C-644 , 2021E-023 , 2021C-559 ; T.I.: 2019C-715 , 2020C-778 , 2021C-733 ).
Publisher Copyright:
© 2022 The Authors
PY - 2022/10/21
Y1 - 2022/10/21
N2 - Cholesterol, one of the major cell membrane components, stabilizes membrane fluidity and regulates signal transduction. Beside its canonical roles, cholesterol has been reported to directly activate signaling pathways such as hedgehog (Hh). We recently found that astrocytes, one of the glial cells, respond to Hh pathway stimulation by Ca signaling. These notions led us to test if extracellularly applied cholesterol triggers Ca signaling in astrocytes. Here, we found that cholesterol application induces robust Ca oscillation only in astrocytes with different properties from the Hh-induced Ca response. The Ca oscillation has a long delay which corresponds to the onset of cholesterol accumulation in the plasma membrane. Blockade of the Ca oscillation resulted in enhancement of astrocytic cell death and disturbance of lipid droplet formation, implying a possibility that the cholesterol-induced Ca oscillation plays important roles in astrocytic survival and cholesterol handling under pathological conditions of cholesterol load such as demyelination.
AB - Cholesterol, one of the major cell membrane components, stabilizes membrane fluidity and regulates signal transduction. Beside its canonical roles, cholesterol has been reported to directly activate signaling pathways such as hedgehog (Hh). We recently found that astrocytes, one of the glial cells, respond to Hh pathway stimulation by Ca signaling. These notions led us to test if extracellularly applied cholesterol triggers Ca signaling in astrocytes. Here, we found that cholesterol application induces robust Ca oscillation only in astrocytes with different properties from the Hh-induced Ca response. The Ca oscillation has a long delay which corresponds to the onset of cholesterol accumulation in the plasma membrane. Blockade of the Ca oscillation resulted in enhancement of astrocytic cell death and disturbance of lipid droplet formation, implying a possibility that the cholesterol-induced Ca oscillation plays important roles in astrocytic survival and cholesterol handling under pathological conditions of cholesterol load such as demyelination.
KW - Biological sciences
KW - Molecular neuroscience
KW - Neuroscience
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U2 - 10.1016/j.isci.2022.105138
DO - 10.1016/j.isci.2022.105138
M3 - Article
AN - SCOPUS:85138779500
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 10
M1 - 105138
ER -