Deoxycholic Acid Induces Intracellular Signaling through Membrane Perturbations Export

@article{citeulike:881589, abstract = {10.1074/jbc.M506710200 Secondary bile acids have long been postulated to be tumor promoters in the colon; however, their mechanism of action remains unclear. In this study, we examined the actions of bile acids at the cell membrane and found that they can perturb membrane structure by alteration of membrane microdomains. Depletion of membrane cholesterol by treating with methyl-\^{I}²-cyclodextrin suppressed deoxycholic acid (DCA)-induced apoptosis, and staining for cholesterol with filipin showed that DCA caused a marked rearrangement of this lipid in the membrane. Likewise, DCA was found to affect membrane distribution of caveolin-1, a marker protein that is enriched in caveolae membrane microdomains. Additionally, fluorescence anisotropy revealed that DCA causes a decrease in membrane fluidity consistent with the increase in membrane cholesterol content observed after 4 h of DCA treatment of HCT116 cells. Significantly, by using radiolabeled bile acids, we found that bile acids are able to interact with and localize to microdomains differently depending on their physicochemical properties. DCA was also found to induce tyrosine phosphorylation and activate the receptor tyrosine kinase epidermal growth factor receptor in a ligand-independent manner. In contrast, ursodeoxycholic acid did not exhibit any of these effects even though it interacted significantly with the microdomains. Collectively, these data suggest that bile acid-induced signaling is initiated through alterations of the plasma membrane structure and the redistribution of cholesterol.}, author = {Jean-Louis, Samira and Akare, Sandeep and Ali, M. Ahad and Mash, Eugene A. and Meuillet, Emmanuelle and Martinez, Jesse D.}, citeulike-article-id = {881589}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M506710200}, citeulike-linkout-1 = {http://www.jbc.org/content/281/21/14948.abstract}, citeulike-linkout-2 = {http://www.jbc.org/content/281/21/14948.full.pdf}, citeulike-linkout-3 = {http://www.jbc.org/cgi/content/abstract/281/21/14948}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/16547009}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=16547009}, day = {26}, doi = {10.1074/jbc.M506710200}, journal = {Journal of Biological Chemistry}, keywords = {acid, apoptosis, cells, deoxycholic, detergent, jeanl06pdf, membrane, peturbation, signalling}, month = {May}, number = {21}, pages = {14948--14960}, posted-at = {2009-11-04 19:04:02}, priority = {2}, title = {Deoxycholic Acid Induces Intracellular Signaling through Membrane Perturbations}, url = {http://dx.doi.org/10.1074/jbc.M506710200}, volume = {281}, year = {2006} }

TY - JOUR ID - citeulike:881589 L3 - citeulike-article-id:881589 N2 - 10.1074/jbc.M506710200 Secondary bile acids have long been postulated to be tumor promoters in the colon; however, their mechanism of action remains unclear. In this study, we examined the actions of bile acids at the cell membrane and found that they can perturb membrane structure by alteration of membrane microdomains. Depletion of membrane cholesterol by treating with methyl-β-cyclodextrin suppressed deoxycholic acid (DCA)-induced apoptosis, and staining for cholesterol with filipin showed that DCA caused a marked rearrangement of this lipid in the membrane. Likewise, DCA was found to affect membrane distribution of caveolin-1, a marker protein that is enriched in caveolae membrane microdomains. Additionally, fluorescence anisotropy revealed that DCA causes a decrease in membrane fluidity consistent with the increase in membrane cholesterol content observed after 4 h of DCA treatment of HCT116 cells. Significantly, by using radiolabeled bile acids, we found that bile acids are able to interact with and localize to microdomains differently depending on their physicochemical properties. DCA was also found to induce tyrosine phosphorylation and activate the receptor tyrosine kinase epidermal growth factor receptor in a ligand-independent manner. In contrast, ursodeoxycholic acid did not exhibit any of these effects even though it interacted significantly with the microdomains. Collectively, these data suggest that bile acid-induced signaling is initiated through alterations of the plasma membrane structure and the redistribution of cholesterol. IS - 21 JF - Journal of Biological Chemistry EP - 14960 TI - Deoxycholic Acid Induces Intracellular Signaling through Membrane Perturbations VL - 281 SP - 14948 KW - acid KW - apoptosis KW - cells KW - deoxycholic KW - detergent KW - jeanl06pdf KW - membrane KW - peturbation KW - signalling AU - Jean-Louis, Samira AU - Akare, Sandeep AU - Ali, Ahad AU - Mash, Eugene AU - Meuillet, Emmanuelle AU - Martinez, Jesse PY - 2006/05/26/ UR - http://dx.doi.org/10.1074/jbc.M506710200 ER -