A quest for the upstream activators of ochratoxin a (OTA)- induced MAPK/ERK1/2
| dc.contributor | Graduate Program in Molecular Biology and Genetics. | |
| dc.contributor.advisor | Yaman, İbrahim . | |
| dc.contributor.author | Gül, Gizem. | |
| dc.date.accessioned | 2023-03-16T11:25:35Z | |
| dc.date.available | 2023-03-16T11:25:35Z | |
| dc.date.issued | 2016. | |
| dc.description.abstract | Ochratoxin-A (OTA) is a mycotoxin, produced as a secondary metabolite by fungi belonging to Aspergillus and Penicillium genera. It has been recognized as a carcinogen in rodents and a possible carcinogen to humans. In our previous study, we demonstrated that OTA induces sustained MAPK/ERK1/2 activation in HK-2 cell line. Upstream activator of ERK1/2 protein activation remained obscure. In this study we screened a number of proteins via Western blot to determine if they cause ERK1/2 activation in OTA-exposed HK-2 cell line. We observed no dramatic increase in the expression levels of neither Integrin and subunits nor Integrin Linked Kinase (ILK). Also there was no discernable increase in the phosphorylation of Focal Adhesion Kinase (FAK) residues that might be involved in OTA mediated ERK1/2 activation under the experimental conditions employed in this study. Although a stable level of PKC phosphorylation was not observed, inhibition of various PKC isoforms reduced OTA-induced ERK1/2 activation. These results suggest PKC as a possible upstream activator in the activation of MAPK/ERK1/2 in OTA-treated HK-2 cells. Moreover, modulation of G protein-coupled receptor (GPCR)-dependent signaling through pertussis and cholera toxins suppressed ERK1/2 activation in response to OTA treatment. In addition, chemical agents that increase intracellular cAMP levels subdued OTA-induced ERK1/2 activation considerably. We also observed that H- 89, a cAMP-dependent kinase (PKA) inhibitor, augments OTA-induced activation of ERK1/2. Taken all together, this study suggests that OTA may cause stimulation of a putative GPCR that results in a decrease in intracellular cAMP levels and ultimately activation of MAPK/ERK1/2 in HK-2 cell line where PKC may be an intermediary in relaying signal from GPCR to ERK1/2. | |
| dc.format.extent | 30 cm. | |
| dc.format.pages | xvii, 80 leaves ; | |
| dc.identifier.other | BIO 2016 G86 | |
| dc.identifier.uri | https://digitalarchive.library.bogazici.edu.tr/handle/123456789/15356 | |
| dc.publisher | Thesis (M.S.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2016. | |
| dc.subject.lcsh | Ochratoxin. | |
| dc.title | A quest for the upstream activators of ochratoxin a (OTA)- induced MAPK/ERK1/2 |
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