Department of Anatomy, St Marianna University School of Medicine, Kawasaki, Japan.
PLoS One. 2012;7(8):e42885. doi: 10.1371/journal.pone.0042885. Epub 2012 Aug 7.
Resealing of a disrupted plasma membrane at the micron-diameter range requires Ca(2+)-regulated exocytosis. Repeated membrane disruptions reseal more quickly than the initial wound, and this potentiation of membrane resealing persists for at least 24 hours after the initial wound. Long-term potentiation of membrane resealing requires CREB-dependent gene expression, which is activated by the PKC- and p38 MAPK-dependent pathway in a wounded cell. The present study demonstrates that membrane resealing is potentiated in both wounded and neighboring cells in MDCK cells. Wounding of cells expressing CREB133, a mutant variant of CREB, does not show the potentiated response of cell membrane resealing in either wounded or neighboring cells. Furthermore, wounding of cells induces CREB phosphorylation, not only in wounded cells, but also in neighboring cells. Inhibition of the nitric oxide/PKG signaling pathway suppresses CREB phosphorylation in neighboring cells, but not in wounded cells. The potentiation of membrane resealing in neighboring cells is suppressed if the nitric oxide/PKG pathway is inhibited during the initial wound. Together, these results suggest that the nitric oxide/PKG pathway stimulates CREB phosphorylation in neighboring cells so that subsequent cell membrane disruptions of the neighboring cells reseal more quickly.
在微米直径范围内，破裂的质膜的重新密封需要 Ca(2+)-调节的胞吐作用。重复的膜破裂比初始伤口更快地重新密封，并且这种膜重新密封的增强作用在初始伤口后至少持续 24 小时。膜重新密封的长期增强需要 CREB 依赖性基因表达，这是由 PKC 和 p38 MAPK 依赖性途径在受伤细胞中激活的。本研究表明，在 MDCK 细胞中，受伤细胞和相邻细胞中的膜重新密封都得到增强。表达 CREB133（CREB 的突变变体）的细胞的损伤不会显示出受伤或相邻细胞中质膜重新密封的增强反应。此外，细胞损伤不仅在受伤细胞中，而且在相邻细胞中诱导 CREB 磷酸化。抑制一氧化氮/PKG 信号通路会抑制相邻细胞中的 CREB 磷酸化，但不会抑制受伤细胞中的 CREB 磷酸化。如果在初始伤口期间抑制一氧化氮/PKG 途径，则会抑制相邻细胞中膜重新密封的增强。总之，这些结果表明，一氧化氮/PKG 途径刺激相邻细胞中的 CREB 磷酸化，从而使相邻细胞的后续细胞膜破裂更快地重新密封。
