Calcineurin (CN) is thought to play a role in the synaptic plastivity and long-term potentiation (LTP) in the hippocampus. Based on two LTP models in vivo, a specific inhibitor cyclosporin A (CsA) of CN was observed, which affected LTP in the hippocampal dentate gyrus of the rats. The results indicated that CsA blocked LTP induced by high frequency stimulation (HFS) partly, but it had no effect on the decrease of the onset and peak latency of population spikes (PS) except that it reduced the increase of the amplitude after HFS. On the other hand, CsA blocked LTP induced by ginsenosides (GSS) completely. It suppressed the GSS-enhanced amplitude of PS reversibly and blocked the decrease of the peak latency of PS induced by the GSS. These results suggest that the postsynaptic CN plays a role in the induction of LTP in the hippocampus of the rats.
钙调神经磷酸酶（calcineurin,CN）被认为在突触可塑性及在海马长时程增强（long term potentiation,LTP）中发挥了一定的作用.在两种整体LTP模型的基础上,观察了CN特异性抑制剂环胞菌素A（cyclosporin A,CsA）对大鼠海马齿状回LTP的影响.CsA能部分阻断高频刺激诱发的LTP,但它只减小了群峰电位（population spikes,PS）幅度的增加,对PS潜伏期的缩短没有影响.另一方面,CsA能完全阻断人参皂甙诱发的LTP,不仅抑制了PS幅度的增加,也阻断了PS潜伏期的缩短.结果提示,突触后神经元的CN在海马LTP的诱发过程中起着重要的作用.
Lactate dehydrogenase A (LDHA) is a well-characterized tetrameric enzyme. Its N-terminal arm, comprised of an α-helix and a p-strand, was suggested to be essential for subunit interactions. To examine the critical amino acid residues in the N-terminus involved in the subunit association, two single-point mutants, Leu3Pro (L3P) and IIe8GIu (I8E), have been constructed. We compared the stability of WT-LDHA (WT) and its variants by unfolding experiments. For WT, a dimeric but inactive intermediate was observed by size-exclusion chromatography at 0.6-0.8 mol/L GdmCI. Leu3Pro exists in an active tetrameric structure in aqueous solution as WT does, but it dissociates into dimers under lower concentration of GdmCI (0.2 mol/L). In aqueous solution, the lle8GIu variant exists predominantly in the dimeric form with increased KM and decreased kcat as compared with those of WT and L3P. However, the activity of lle8GIu increases significantly in the presence of sodium sulfate. In conclusion, two mutants are less stable than WT in oligomer structure. Results also support the fact that some residues in the N-terminal arm, especially the Leu8 in the p-structure, contribute the important binding energies to the dimerization of dimers, which might affect the assembly of the enzyme as well as the catalytic function.
