Murphy Kaitlin C, Morgan Joshua T, Wood Joshua A, Sadeli Adeline, Murphy Christopher J, Russell Paul
Department of Biomedical Engineering / University of California, Davis.
Department of Surgical and Radiological Sciences, School of Veterinary Medicine / University of California, Davis.
Exp Cell Res. 2014 Oct 15;328(1):164-171. doi: 10.1016/j.yexcr.2014.06.014. Epub 2014 Jun 30.
The cytoskeleton of human trabecular meshwork (HTM) cells is known to be altered in glaucoma and has been hypothesized to reduce outflow facility through contracting the HTM tissue. Latrunculin B (Lat-B) and Rho-associated protein kinase (ROCK) inhibitors disrupt the actin cytoskeleton and are in clinical trials as glaucoma therapeutics. We have previously reported a transient increase in HTM cell stiffness peaking at 90 min after Lat-B treatment with a return to pretreatment values after 270 min. We hypothesize that changes in actin morphology correlate with alterations in cell stiffness induced by Lat-B but this is not a general consequence of other cytoskeletal disrupting agents such as Rho kinase inhibitors. We treated HTM cells with 2 µM Lat-B or 100 µM Y-27632 and allowed the cells to recover for 30-270 min. While examining actin morphology in Lat-B treated cells, we observed striking cortical actin arrays (CAAs). The percentage of CAA positive cells (CPCs) was time dependent and exceeded 30% at 90 min and decreased after 270 min. Y-27632 treated cells exhibited few CAAs and no changes in cell stiffness. Together, these data suggest that the increase in cell stiffness after Lat-B treatment is correlated with CAAs.
已知青光眼患者人小梁网(HTM)细胞的细胞骨架会发生改变,并且据推测这会通过收缩HTM组织来降低房水流出易度。Latrunculin B(Lat - B)和Rho相关蛋白激酶(ROCK)抑制剂会破坏肌动蛋白细胞骨架,目前正作为青光眼治疗药物进行临床试验。我们之前报道过,Lat - B处理后90分钟HTM细胞硬度会短暂增加并达到峰值,270分钟后恢复到预处理值。我们推测肌动蛋白形态的变化与Lat - B诱导的细胞硬度改变相关,但这并非其他细胞骨架破坏剂(如Rho激酶抑制剂)的普遍结果。我们用2 μM Lat - B或100 μM Y - 27632处理HTM细胞,并让细胞恢复30 - 270分钟。在检查Lat - B处理细胞的肌动蛋白形态时,我们观察到显著的皮质肌动蛋白阵列(CAA)。CAA阳性细胞(CPC)的百分比呈时间依赖性,在90分钟时超过30%,270分钟后下降。Y - 27632处理的细胞几乎没有CAA,细胞硬度也没有变化。总之,这些数据表明Lat - B处理后细胞硬度的增加与CAA相关。