کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6262954 1613817 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ReportHint1 knockout results in a compromised activation of protein kinase C gamma in the brain
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Research ReportHint1 knockout results in a compromised activation of protein kinase C gamma in the brain
چکیده انگلیسی


- The protein abundance and activity of PKCγ in Hint1-deficient brain was defined.
- Hint1 deficiency leads to an increased protein level of PKCγ in mouse brain.
- PKCγ in Hint1 deficient brain keeps a basal activity in normal condition.
- Hint1 deficiency results in a compromised activation of PKCγ in mouse brain.

Previous studies have implicated a role of the histidine triad nucleotide-binding protein 1 (Hint1) in the pathogenesis of schizophrenia. Protein kinase C gamma (PKCγ) could be potentially involved in the Hint1-implicated pathogenesis since PKCγ was identified as a Hint1 interacting protein. Recently, a debate was brought forward from the understanding how Hint1 affects the expression and activity of PKCγ in the brain. In the present study, we use Hint1 knockout mice and biochemical analysis to define the effect of Hint1 on protein PKCγ. Our data reveal that Hint1-deficiency in mouse brains led to increased protein levels of PKCγ in the cortex and hippocampus, the striatum and thalamus and amygdala. Without stimulation, PKCγ protein in Hint1-deficient brain displayed a basal activity that was reflected by control-leveled phosphorylations of PKCγ T514 and T674 at its kinase domain. Upon psycho-stimulation, both sites of PKCγ T514 and T674 were activated in these brain structures via phosphorylation; however, the phosphorylation level at the site of PKCγ T674 apparently attenuated in Hint1-deficient mice compared to wild-type control. Thus, we conclude that Hint1 deficiency leads to an increased protein level of PKCγ in the brain and a compromised activation response of PKCγ upon stimulation. These findings suggest an inhibitory role of Hint1 on the protein PKCγ in the brain and an impaired PKCγ-mediated phosphorylation signal in Hint1-deficient neuron.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1622, 5 October 2015, Pages 196-203
نویسندگان
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