Okamoto Takashi, Namikawa Kazuhiko, Asano Tomoichiro, Takaoka Kunio, Kiyama Hiroshi
Department of Anatomy and Neurobiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
Brain Res Mol Brain Res. 2004 Nov 24;131(1-2):119-25. doi: 10.1016/j.molbrainres.2004.08.015.
Type Ia phosphatidylinositol 3-kinase (PI3K) generates lipid products that operate as one of major second messengers following activation of tyrosine kinase receptors. PI3K is a heterodimer composed of a 110-kDa catalytic subunit and a regulatory subunit. In this study, we determined the expression of mRNA for the regulatory subunits after injury of rat hypoglossal nerves. In situ hybridization histochemistry revealed that the expression of PI3K regulatory subunit alpha isoforms (p85alpha, p55alpha, and p50alpha) was significantly enhanced in injured motor neurons, whereas other regulatory subunits such as p85beta or p55gamma were not detected. Of the alpha isoforms, the greatest increase was observed in p55alpha mRNA levels, while there were smaller increases in p85alpha and p50alpha mRNA expression. These results were confirmed by RT-PCR analysis. Further immunohistochemical analysis also confirmed the increased level of p55alpha protein in injured motor neurons. Taken together with the previously reported induction of the p110alpha catalytic subunit in injured neurons, these results suggest that PI3K, consisting of p55alpha and p110alpha, plays a crucial role in the process of nerve regeneration.
I型磷脂酰肌醇3激酶（PI3K）产生脂质产物，这些产物在酪氨酸激酶受体激活后作为主要的第二信使之一发挥作用。PI3K是一种异二聚体，由一个110 kDa的催化亚基和一个调节亚基组成。在本研究中，我们测定了大鼠舌下神经损伤后调节亚基的mRNA表达。原位杂交组织化学显示，PI3K调节亚基α亚型（p85α、p55α和p50α）在损伤的运动神经元中的表达显著增强，而未检测到其他调节亚基，如p85β或p55γ。在α亚型中，p55α mRNA水平升高最为明显，而p85α和p50α mRNA表达升高幅度较小。这些结果通过逆转录聚合酶链反应（RT-PCR）分析得到证实。进一步的免疫组织化学分析也证实了损伤的运动神经元中p55α蛋白水平升高。结合先前报道的损伤神经元中p110α催化亚基的诱导，这些结果表明由p55α和p110α组成的PI3K在神经再生过程中起关键作用。
