You are here:
In vivo Assessment and Potential Diagnosis of Xenobiotics that Perturb the Thyroid Pathway: Proteomic Analysis of Xenopus laevis Brain Tissue following Exposure to Model T4 Inhibitors
Citation:
SERRANO, J. A., L. HIGGINS, B. A. WITTHUHN, L. B. ANDERSON, G. W. HOLCOMBE, P. A. KOSIAN, J. J. KORTE, J. E. TIETGE, AND S. J. DEGITZ. In vivo Assessment and Potential Diagnosis of Xenobiotics that Perturb the Thyroid Pathway: Proteomic Analysis of Xenopus laevis Brain Tissue following Exposure to Model T4 Inhibitors. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY - PART D: GENOMICS AND PROTEOMICS. Elsevier BV, AMSTERDAM, Netherlands, 5(2):138-150, (2010).
Impact/Purpose:
To document research results.
Description:
As part of a multi-endpoint systems approach to develop comprehensive methods for assessing endocrine stressors in vertebrates, differential protein profiling was used to investigate expression profiles in the brain of an amphibian model (Xenopus laevis) following in vivo exposure to a suite of T4 synthesis inhibitors. We specifically address the application of 2D PAGE, iTRAQ-labeling and LC-MS/MS technologies to assess changes in relative protein expression levels as a potential way to screen chemicals for endocrine activity in anuran species. Analysis of pituitary protein expression profiles was not experimentally feasible, but empirically establishing a database of pituitary-located proteins allowed a means to distinguish proteins that were altered by T4 inhibitors in total brain and potentially in pituitary tissue. 2D PAGE and iTRAQ proved to be effective complementary techniques for distinguishing and assessing protein profiles in small amounts of tissues critical to the vertebrate hypothalamohypohysialthyroid axis (HPT) compensatory response to T4 synthesis inhibition. Correlation of molecular information to other cellular and organism-level responses would facilitate development of a cost-effective, non-mammalian screening assay for thyroid axis-disrupting chemicals as mandated by the USEPA.