Stress-responsive gene TauT and acute kidney injury

Autor: Russell W. Chesney, Xiaobin Han
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Male
animal structures
Taurine
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Molecular Sequence Data
Down-Regulation
Antineoplastic Agents
Apoptosis
Mice
Transgenic
Review
Biology
urologic and male genital diseases
Kidney
Nephrotoxicity
Cell Line
Mice
In vivo
Genes
Reporter
medicine
Animals
Pharmacology (medical)
Promoter Regions
Genetic
Molecular Biology
Taurine transport
Biochemistry
medical
Regulation of gene expression
Cisplatin
Membrane Glycoproteins
Base Sequence
Biochemistry (medical)
Acute kidney injury
JNK Mitogen-Activated Protein Kinases
Kidney metabolism
Membrane Transport Proteins
Cell Biology
General Medicine
Acute Kidney Injury
medicine.disease
Genes
p53
Molecular biology
medicine.anatomical_structure
Gene Expression Regulation
Cancer research
medicine.drug
Signal Transduction
Zdroj: Journal of Biomedical Science
ISSN: 1423-0127
1021-7770
Popis: Background Cisplatin is a commonly used chemotherapeutic agent that has a major limitation because of its nephrotoxicity. We have demonstrated that cisplatin down-regulates the expression of the taurine transporter gene (TauT) in renal cells and that forced overexpression of TauT protects against cisplatin-induced apoptosis in renal cells in vitro and in vivo. In the present study, we have investigated how TauT is regulated by p53 and c-Jun and its role during acute kidney injury (AKI). Methods Regulation of TauT by p53 and c-Jun was determined by reporter gene assay, DNA binding, Western blot analysis, and immunohistochemistry. Results TauT was down-regulated by p53 and up-regulated by c-Jun. Two potential binding sites for c-Jun were identified in the promoter region of TauT. Inhibition of c-Jun N-terminal kinase (JNK) enhanced TauT promoter activity. Overexpression of TauT protects against cisplatin-induced kidney injury in a TauT transgenic mouse model. Conclusions Our findings suggest that TauT plays a critical role in renal function. Expression of TauT is negatively regulated by p53 and positively regulated by c-Jun, which is mediated by the JNK signaling pathway. The outcome level of TauT may determine the fate of renal cells during stress-induced AKI.
Databáze: OpenAIRE
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