Back to Search
Start Over
Mitochondrial perturbation attenuates bile acid-induced cytotoxicity.
- Source :
-
Cell biology and toxicology [Cell Biol Toxicol] 2005 Sep-Nov; Vol. 21 (5-6), pp. 215-31. - Publication Year :
- 2005
-
Abstract
- Hydrophobic bile acids such as deoxycholate (DOC) are known to damage liver cells during cholestasis and promote colon cancer. Cellular stresses induced by bile acids, which include mitochondrial and endoplasmic reticulum (ER) stresses, can result in apoptosis. We found that inhibition of mitochondrial complexes I-V with rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, myxothiazol or oligomycin strongly protected against DOC-induced apoptosis of HCT-116 cells. To understand the mechanism of this protection, we explored the ability of these specific inhibitors to reduce DOC-induced mitochondrial and ER stresses. Different inhibitors markedly reduced DOC-induction of mitochondrial condensation, the DOC-induced decrease in mitochondrial membrane potential and the DOC-induced dilatation of the ER (evidence of ER stress). A dramatic induction of nucleolar segregation by antimycin A and myxothiazol, two distinct complex III inhibitors, was also observed. These findings strongly implicate mitochondrial crosstalk with apoptotic signaling pathways and mitochondrial-nucleolar crosstalk in the development of apoptosis resistance in the colon.
- Subjects :
- Antimycin A pharmacology
Bile Acids and Salts toxicity
Cell Nucleolus drug effects
Cell Nucleolus ultrastructure
Electron Transport Complex III metabolism
Endoplasmic Reticulum drug effects
Endoplasmic Reticulum ultrastructure
HCT116 Cells
Humans
Membrane Potentials
Methacrylates pharmacology
Microscopy, Electron, Transmission
Mitochondria metabolism
Mitochondrial Proton-Translocating ATPases metabolism
Mitochondrial Swelling
Oligomycins pharmacology
Thiazoles pharmacology
Time Factors
Uncoupling Agents pharmacology
Apoptosis drug effects
Deoxycholic Acid toxicity
Mitochondria drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0742-2091
- Volume :
- 21
- Issue :
- 5-6
- Database :
- MEDLINE
- Journal :
- Cell biology and toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 16323058
- Full Text :
- https://doi.org/10.1007/s10565-005-0166-6