LIMK1 and LIMK2 regulate the actin cytoskeleton by phosphorylating and inactivating the cofilin family of actin-depolymerizing factors; LIMK1 also acts to destabilize microtubules and regulates cell motility, including tumor metastasis[3]. BMS-5 is a potent LIMK inhibitor with IC50s of 7 nM and 8 nM for LIMK1 and LIMK2, respectively[3]. BMS-5 inhibits cofilin-Ser3 phosphorylation in a dose-dependent manner in Nf2ΔEx2 mouse Schwann cells (MSCs) with an IC50 of ~2 µM, and it reduces Nf2ΔEx2 MSC viability in a dose-dependent manner with an IC50 of 3.9 µM, but does not significantly reduce the viability of control Nf2flox2/flox2 MSCs at equivalent BMS-5 concentrations. At 10 µM BMS-5, Nf2ΔEx2 MSC viability is 40% compared to 83% for controls[4]. BMS-5 (20 or 200 μM/side) or vehicle is bilaterally infused into the hippocampus of rats immediately after contextual fear conditioning training. Rats are tested for memory consolidation 48 h after fear conditioning. Post hoc analysis shows that the group treated with 200 μM BMS-5 expresses lower freezing levels compared to the 20 μM and vehicle groups (P < 0.01). An additional experiment is performed in order to test if a short-term fear memory (STM) could be affected by LIMK inhibition. Animals are infused with 200 μM BMS-5 immediately after training and are tested in the same context 2 h later. No significant difference is found between both groups, BMS-5 and vehicle, in the test, suggesting that actin dynamics briefly after training is not crucial to STM expression[5].
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