Clos J, Dicou E
URA 1197 du CNRS, Université Montpellier II, France.
Brain Res Dev Brain Res. 1997 Apr 18;99(2):267-70. doi: 10.1016/s0165-3806(97)00005-9.
LIP1, a 29-amino acid (aa) peptide, and LIP2, a 38aa peptide, corresponding to sequences within the nerve growth factor (NGF) precursor that are flanked by basic amino acid processing sites, were shown to be present in the rat intestine and to induce in PC12 cells several early cellular events, such as F-actin rearrangement and tyrosine phosphorylation of the Trk protein. In this report, we provide evidence that the two propeptides can affect cholinergic enzyme activities in vivo. Intracerebroventricular injections of LIP1 or LIP2 in neonatal hypothyroid rats significantly increased choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in forebrain regions with an apparent regional specificity. Moreover, antibodies against LIP1 or LIP2 injected intracerebroventricularly in neonatal rats significantly decreased ChAT and AChE in the same regions of the brain. These data suggest a physiological role for the two propeptides derived from the proNGF in the development of forebrain cholinergic neurons.
LIP1是一种含29个氨基酸的肽,LIP2是一种含38个氨基酸的肽,它们对应于神经生长因子(NGF)前体中两侧带有碱性氨基酸加工位点的序列,已证实在大鼠肠道中存在,并能在PC12细胞中诱导多种早期细胞事件,如F-肌动蛋白重排和Trk蛋白的酪氨酸磷酸化。在本报告中,我们提供证据表明这两种前体肽可在体内影响胆碱能酶活性。向新生甲状腺功能减退大鼠脑室内注射LIP1或LIP2可显著增加前脑区域胆碱乙酰转移酶(ChAT)和乙酰胆碱酯酶(AChE)的活性,且具有明显的区域特异性。此外,向新生大鼠脑室内注射抗LIP1或LIP2抗体可显著降低大脑相同区域的ChAT和AChE。这些数据表明源自前体NGF的这两种前体肽在前脑胆碱能神经元发育中具有生理作用。