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1.
J Avian Med Surg ; 30(2): 122-6, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27315378

ABSTRACT

Clinical signs of organophosphate and carbamate intoxication in wild birds can be mistaken for those of other diseases, thus potentially delaying diagnosis and implementation of life-saving treatment. The objective of this study was to determine the reference interval for blood cholinesterase activity in 20 different wild avian species from 7 different orders, thereby compiling a reference database for wildlife veterinarians. Blood was collected from birds not suspected of having organophosphate or carbamate toxicosis, and the modified Michel method, which determines the change in blood pH that directly correlates with cholinesterase activity, was used to measure blood cholinesterase levels. Results of change in blood pH values ranged from 0.11 for the white-tailed eagle ( Haliaeetus albicilla ) to 0.90 for the honey buzzard ( Pernis apivorus ). The results showed that even within the same family, interspecies differences in normal cholinesterase blood activity were not uncommon. The findings emphasized the importance of determining reference intervals for avian blood cholinesterase activity at the species level.


Subject(s)
Animals, Wild , Birds/blood , Cholinesterases/blood , Animals , Birds/classification , Species Specificity
2.
J Biol Chem ; 286(22): 19381-91, 2011 Jun 03.
Article in English | MEDLINE | ID: mdl-21489989

ABSTRACT

Testicular cancer is highly curable with cisplatin-based therapy, and testicular cancer-derived human embryonal carcinoma (EC) cells undergo a p53-dominant transcriptional response to cisplatin. In this study, we have discovered that a poorly characterized member of the death-associated protein family of serine/threonine kinases, STK17A (also called DRAK1), is a novel p53 target gene. Cisplatin-mediated induction of STK17A in the EC cell line NT2/D1 was prevented with p53 siRNA. Furthermore, STK17A was induced with cisplatin in HCT116 and MCF10A cells but to a much lesser extent in isogenic p53-suppressed cells. A functional p53 response element that binds endogenous p53 in a cisplatin-dependent manner was identified 5 kb upstream of the first coding exon of STK17A. STK17A is not present in the mouse genome, but the closely related gene STK17B is induced with cisplatin in mouse NIH3T3 cells, although this induction is p53-independent. Interestingly, in human cells containing both STK17A and STK17B, only STK17A is induced with cisplatin. Knockdown of STK17A conferred resistance to cisplatin-induced growth suppression and apoptotic cell death in EC cells. This was associated with the up-regulation of detoxifying and antioxidant genes, including metallothioneins MT1H, MT1M, and MT1X that have previously been implicated in cisplatin resistance. In addition, knockdown of STK17A resulted in decreased cellular reactive oxygen species, whereas STK17A overexpression increased reactive oxygen species. In summary, we have identified STK17A as a novel direct target of p53 and a modulator of cisplatin toxicity and reactive oxygen species in testicular cancer cells.


Subject(s)
Apoptosis Regulatory Proteins/biosynthesis , Carcinoma, Embryonal/metabolism , Drug Resistance, Neoplasm , Protein Serine-Threonine Kinases/biosynthesis , Reactive Oxygen Species/metabolism , Testicular Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Antineoplastic Agents/pharmacology , Apoptosis Regulatory Proteins/genetics , Carcinoma, Embryonal/drug therapy , Carcinoma, Embryonal/genetics , Cell Line, Tumor , Cisplatin/pharmacology , Gene Knockdown Techniques , Humans , Male , Metallothionein , Mice , NIH 3T3 Cells , Protein Serine-Threonine Kinases/genetics , Response Elements/genetics , Species Specificity , Testicular Neoplasms/genetics , Tumor Suppressor Protein p53/genetics
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