Jensen J B, Shimon H, Mørk A
Department of Clinical Biochemistry, Bispebjerg Hospital, Copenhagen, Denmark.
J Neural Transm (Vienna). 2000;107(4):501-9. doi: 10.1007/s007020070091.
Abnormal phosphorylation has been proposed to be involved in the pathogenesis of affective disorders. The present study investigated basal and cAMP-stimulated endogenous protein phosphorylation in human post-mortem brain tissue from bipolar and schizophrenic patients. Furthermore, basal kinase activity and stimulated protein kinase A activity were measured. The frontal and occipital cortex were analysed. Using [gamma-32P]ATP as phosphate donor, basal and cAMP-stimulated phosphorylation of endogenous proteins was measured in the absence or presence of 8-Br-cAMP, respectively. The proteins were separated on SDS-gels and the radioactivity in the individual bands was measured. We observed a significant reduction of 32P incorporation in three protein substrates (15, 16 and 21 kD) in frontal cortex of bipolar patients. However, there were no differences in the PKA activity between any of the groups. The present study demonstrates abnormal phosphorylation of specific proteins in brain tissue obtained from bipolar patients in comparison to schizophrenics and controls.
异常磷酸化被认为与情感障碍的发病机制有关。本研究调查了双相情感障碍患者和精神分裂症患者死后脑组织中的基础和cAMP刺激的内源性蛋白质磷酸化情况。此外，还测量了基础激酶活性和刺激后的蛋白激酶A活性。对额叶和枕叶皮质进行了分析。以[γ-32P]ATP作为磷酸盐供体，分别在不存在或存在8-溴-cAMP的情况下测量基础和cAMP刺激的内源性蛋白质磷酸化。蛋白质在SDS凝胶上分离，并测量各个条带中的放射性。我们观察到双相情感障碍患者额叶皮质中三种蛋白质底物（15、16和21 kD）的32P掺入量显著降低。然而，任何组之间的蛋白激酶A活性均无差异。本研究表明，与精神分裂症患者和对照组相比，双相情感障碍患者脑组织中特定蛋白质存在异常磷酸化。
