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TCDD induces UbcH7 expression and synphilin‐1 protein degradation in the mouse ventral midbrain
Author(s) -
GonzálezBarbosa Emmanuel,
MejíaGarcía Alejandro,
Bautista Elizabeth,
Gonzalez Frank J.,
Segovia José,
Elizondo Guillermo
Publication year - 2017
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21947
Subject(s) - parkin , aryl hydrocarbon receptor , ubiquitin ligase , microbiology and biotechnology , transactivation , ubiquitin , chemistry , biology , gene expression , biochemistry , transcription factor , gene , parkinson's disease , medicine , disease
UbcH7 is an ubiquitin‐conjugating enzyme that interacts with parkin, an E3 ligase. The UbcH7–parkin complex promotes the ubiquitination and degradation of several proteins via the 26S proteasome. Cellular accumulation of the UbcH7–parkin targets alpha‐synuclein and synphilin‐1 has been associated with Parkinson disease. In mouse liver, 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin, an aryl hydrocarbon receptor ligand, induces UbcH7 expression. Therefore, the aim of the present study was to determine whether 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin induces Ubch7 mRNA and UbcH7 protein expression in the mouse brain, to characterize the molecular mechanism, and the effect on synphilin‐1 half‐life. We found that 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin promotes the aryl hydrocarbon receptor binding to Ubch7 gene promoter as well as its transactivation, resulting in an induction of UbcH7 levels in the olfactory bulb, ventral midbrain, hippocampus, striatum, cerebral cortex, brain stem, and medulla oblongata. In parallel, 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin promoted synphilin‐1 degradation in an aryl hydrocarbon receptor‐dependent way.