Fong Barry, Watson Patricia H, Watson Andrew J
Department of Physiology and Pharmacology, The University of Western Ontario London, Ontario, Canada.
BMC Dev Biol. 2007 Jan 10;7:2. doi: 10.1186/1471-213X-7-2.
Mechanisms that confer an ability to respond positively to environmental osmolarity are fundamental to ensuring embryo survival during the preimplantation period. Activation of p38 mitogen-activated protein kinase (MAPK) occurs following exposure to hyperosmotic treatment. Recently, a novel scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM) was linked to p38 MAPK activation in response to sorbitol-induced hypertonicity. The human ortholog of OSM is cerebral cavernous malformation 2 (CCM2). The present study was conducted to investigate whether CCM2 is expressed during mouse preimplantation development and to determine whether this scaffolding protein is associated with p38 MAPK activation following exposure of preimplantation embryos to hyperosmotic environments.
Our results indicate that Ccm2 along with upstream p38 MAPK pathway constituents (Map3k3, Map2k3, Map2k6, and Map2k4) are expressed throughout mouse preimplantation development. CCM2, MAP3K3 and the phosphorylated forms of MAP2K3/MAP2K6 and MAP2K4 were also detected throughout preimplantation development. Embryo culture in hyperosmotic media increased p38 MAPK activity in conjunction with elevated CCM2 levels.
These results define the expression of upstream activators of p38 MAPK during preimplantation development and indicate that embryo responses to hyperosmotic environments include elevation of CCM2 and activation of p38 MAPK.
赋予对环境渗透压做出积极反应能力的机制对于确保植入前胚胎存活至关重要。暴露于高渗处理后,p38丝裂原活化蛋白激酶(MAPK)会被激活。最近,一种名为MEKK3渗透压传感支架蛋白(OSM)的新型支架蛋白与山梨醇诱导的高渗引起的p38 MAPK激活有关。OSM的人类同源物是脑海绵状血管畸形2(CCM2)。本研究旨在调查CCM2在小鼠植入前发育过程中是否表达,并确定这种支架蛋白在植入前胚胎暴露于高渗环境后是否与p38 MAPK激活相关。
我们的结果表明,Ccm2以及上游p38 MAPK途径成分(Map3k3、Map2k3、Map2k6和Map2k4)在小鼠植入前发育过程中均有表达。在整个植入前发育过程中也检测到了CCM2、MAP3K3以及MAP2K3/MAP2K6和MAP2K4的磷酸化形式。在高渗培养基中培养胚胎会增加p38 MAPK活性,同时CCM2水平升高。
这些结果确定了p38 MAPK上游激活剂在植入前发育过程中的表达,并表明胚胎对高渗环境的反应包括CCM2水平升高和p38 MAPK激活。