Squassina Alessio, Congiu Donatella, Manconi Francesca, Manchia Mirko, Chillotti Caterina, Lampus Simona, Severino Giovanni, Zompo Maria Del
Section of Clinical Pharmacology, Department of Neurosciences B.B. Brodie, University of Cagliari, SS 554, km. 4,500, 09042 Monserrato, Cagliari, Italy.
Pharmacol Res. 2008 May;57(5):369-73. doi: 10.1016/j.phrs.2008.03.011. Epub 2008 Apr 1.
A number of studies support the notion that lithium interacts with the protein kinase C (PKC) pathway, an important mediator of several intracellular responses to neurotransmitter signaling. PDLIM5 (PDZ and LIM domain 5; LIM) is an adaptor protein that selectively binds the isozyme PKC(epsilon) to N-type Ca(2+) channels in neurons. We tested for an association between three single nucleotide polymorphisms (SNPs) at the PDLIM5 gene and lithium prophylaxis in a Sardinian sample comprised of 155 bipolar patients treated with lithium. In order to evaluate whether PDLIM5 expression interacts with lithium response, we carried out gene expression analysis in lymphoblastoid cells of 30 bipolar patients. No association was shown between PDLIM5 polymorphisms and lithium response. When PDLIM5 expression was evaluated, no significant differences were detected between Full Responders to lithium (total score>or=7) and other patients (total score<or=6). Our negative findings do not exclude involvement of PDLIM5 in lithium prophylaxis, and further investigation is warranted.
多项研究支持锂与蛋白激酶C（PKC）途径相互作用的观点，PKC途径是几种细胞内对神经递质信号反应的重要介导因子。PDLIM5（PDZ和LIM结构域5；LIM）是一种衔接蛋白，可选择性地将同工酶PKC（ε）与神经元中的N型钙通道结合。我们在一个由155名接受锂治疗的双相情感障碍患者组成的撒丁岛样本中，测试了PDLIM5基因的三个单核苷酸多态性（SNP）与锂预防之间的关联。为了评估PDLIM-5表达是否与锂反应相互作用，我们对30名双相情感障碍患者的淋巴母细胞进行了基因表达分析。未发现PDLIM5多态性与锂反应之间存在关联。在评估PDLIM5表达时，锂完全反应者（总分≥7）与其他患者（总分≤6）之间未检测到显著差异。我们的阴性结果并不排除PDLIM5参与锂预防，因此有必要进行进一步研究。
