Effects and Mechanisms of Autophagy Induced by Solubilized-Cholesterol in Hepatocytes: A Comparative Study Among Solvents

Effects and Mechanisms of Autophagy Induced by Solubilized-Cholesterol in Hepatocytes: A Comparative Study Among Solvents

Cholesterol, the principal sterol in mammalian cells, has been reported to play a role in the pathogenesis of several diseases through autophagy. Due to its insoluble characteristic, all in vitro cholesterol experiments are performed using dimethyl sulphoxide, methyl-β-cyclodextrin, and ethanol co-s...

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Bibliographic Details
Published in:Cell biochemistry and biophysics Vol. 78; no. 3; pp. 357 - 366
Main Authors: Liang, Dong, Osoro, Ezra K., Tan, Shuai, Lan, Xi, Zhu, Wenhua, Wu, Litao, Du, Xiaojuan, Li, Dongmin, Lu, Shemin
Format: Journal Article
Language:English
Published: New York Springer US 01-09-2020
Springer Nature B.V
Subjects:
AKT protein
Animals
Apoptosis
Autophagy
beta-Cyclodextrins - metabolism
Biochemistry
Biological and Medical Physics
Biomedical and Life Sciences
Biophysics
Biotechnology
Carcinoma, Hepatocellular - metabolism
Caspase 3 - metabolism
Cell Biology
Cell Line, Tumor
Cell Survival
Cholesterol
Cholesterol - chemistry
Comparative studies
Cyclodextrins
Cytotoxicity
Dimethyl sulfoxide
Ethanol
Hepatocytes
Hepatocytes - metabolism
Life Sciences
Liver Neoplasms - metabolism
Lysosomes - metabolism
Mammalian cells
Methyl-β-Cyclodextrin
Microscopy, Electron, Transmission
Microtubule-Associated Proteins - metabolism
Original Paper
Pathogenesis
Phagocytosis
Pharmacology/Toxicology
Pretreatment
Proto-Oncogene Proteins c-akt - metabolism
Rats
Solvents
Solvents - chemistry
TOR protein
TOR Serine-Threonine Kinases - metabolism
Methyl-β-cyclodextrin
Autophagy
Cholesterol
Apoptosis
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Summary:Cholesterol, the principal sterol in mammalian cells, has been reported to play a role in the pathogenesis of several diseases through autophagy. Due to its insoluble characteristic, all in vitro cholesterol experiments are performed using dimethyl sulphoxide, methyl-β-cyclodextrin, and ethanol co-solvents. To investigate whether the types of solvents have different effects on cholesterol-induced cell behaviors, we analyzed the effects and mechanisms of autophagy induced by solubilized-cholesterol in hepatic cells. We found that both solubilized-cholesterol and involved solvents could induce autophagy. Solubilized-cholesterol could further enhance the LC3-II expression with or without the pre-treatment with lysosomal blockers compared with the single-solvent groups, indicating that cholesterol could sensitize cells to solvents-induced autophagy. Besides, solubilized-cholesterol and single-solvent treatment could repress the activation of AKT-mTOR pathway. Furthermore, cholesterol solubilized in methyl-β-cyclodextrin could induce apoptosis while other solubilized-cholesterol or single solvent groups could not, suggesting that different dissolve methods may affect the cytotoxic of cholesterol. These results strongly suggest that the effect of solvent should be taken into consideration in further in vitro cholesterol studies.
Bibliography:ObjectType-Article-2
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content type line 23
ISSN:1085-9195
1559-0283
DOI:10.1007/s12013-020-00917-2