| First Author | Zhang F | Year | 2015 |
| Journal | Brain Res | Volume | 1622 |
| Pages | 196-203 | PubMed ID | 26133792 |
| Mgi Jnum | J:229108 | Mgi Id | MGI:5750816 |
| Doi | 10.1016/j.brainres.2015.06.029 | Citation | Zhang F, et al. (2015) Hint1 knockout results in a compromised activation of protein kinase C gamma in the brain. Brain Res 1622:196-203 |
| abstractText | Previous studies have implicated a role of the histidine triad nucleotide-binding protein 1 (Hint1) in the pathogenesis of schizophrenia. Protein kinase C gamma (PKCgamma) could be potentially involved in the Hint1-implicated pathogenesis since PKCgamma was identified as a Hint1 interacting protein. Recently, a debate was brought forward from the understanding how Hint1 affects the expression and activity of PKCgamma in the brain. In the present study, we use Hint1 knockout mice and biochemical analysis to define the effect of Hint1 on protein PKCgamma. Our data reveal that Hint1-deficiency in mouse brains led to increased protein levels of PKCgamma in the cortex and hippocampus, the striatum and thalamus and amygdala. Without stimulation, PKCgamma protein in Hint1-deficient brain displayed a basal activity that was reflected by control-leveled phosphorylations of PKCgamma T514 and T674 at its kinase domain. Upon psycho-stimulation, both sites of PKCgamma T514 and T674 were activated in these brain structures via phosphorylation; however, the phosphorylation level at the site of PKCgamma 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 PKCgamma in the brain and a compromised activation response of PKCgamma upon stimulation. These findings suggest an inhibitory role of Hint1 on the protein PKCgamma in the brain and an impaired PKCgamma-mediated phosphorylation signal in Hint1-deficient neuron. |
