Furness John B, Hind Anderson J, Ngui Katrina, Robbins Heather L, Clerc Nadine, Merrot Thierry, Tjandra Joseph J, Poole Daniel P
Department of Anatomy and Cell Biology and Centre for Neuroscience, University of Melbourne, Parkville, VIC 3010, Australia.
Histochem Cell Biol. 2006 Nov;126(5):537-48. doi: 10.1007/s00418-006-0190-5. Epub 2006 May 30.
In many organs, different protein kinase C (PKC) isoforms are expressed in specific cell types, suggesting that the different PKCs have cell-specific roles, and also that drugs acting on a particular PKC may have effects on the whole organ that are distinguishable from drugs that target other isoforms. Previous studies of the guinea-pig and mouse intestine indicate that there are cell-specific expressions of PKC isoforms in neurons, muscle and the interstitial cells of Cajal. In the present study we have investigated the expression of different PKCs in human intestine. Immunohistochemical studies showed that the forms that are prominent in human enteric neurons are PKCs gamma and epsilon and in muscle the dominant form is PKCdelta. Neurons were weakly stained for PKCbetaI. These observations parallel findings in guinea-pig and mouse, except that in human PKCgamma-IR was not present in the same types of neurons that express it in the guinea-pig. Enteric glial cells were strongly immunoreactive for PKCalpha, which is also the major isoform in enteric glial cells of guinea-pig. In human and guinea-pig, glial cells also express PKCbetaI. Spindle-shaped cells in the mucosa were immunoreactive for PKCalpha and PKCgamma and in the muscle layers similar cells had PKCgamma-IR and PKCtheta-IR. The spindle-shaped cells were similar in morphology to interstitial cells of Cajal. Western analysis and RT-PCR confirmed the presence of the PKC isoform proteins and mRNA in the tissue. We conclude that there is cell-type specific expression of different PKCs in enteric neurons and intestinal muscle in human tissue, and that there are strong similarities in patterns of expression between laboratory animals and human, but some clear differences are also observed.
在许多器官中，不同的蛋白激酶C（PKC）亚型在特定细胞类型中表达，这表明不同的PKC具有细胞特异性作用，而且作用于特定PKC的药物对整个器官产生的影响可能与作用于其他亚型的药物不同。先前对豚鼠和小鼠肠道的研究表明，PKC亚型在神经元、肌肉和 Cajal 间质细胞中存在细胞特异性表达。在本研究中，我们调查了不同PKC在人肠道中的表达。免疫组织化学研究表明，在人肠神经元中突出的形式是PKCγ和ε，在肌肉中占主导地位的形式是PKCδ。神经元对PKCβI染色较弱。这些观察结果与豚鼠和小鼠的发现相似，只是在人类中，PKCγ免疫反应性不存在于豚鼠中表达它的相同类型的神经元中。肠胶质细胞对PKCα有强烈的免疫反应，PKCα也是豚鼠肠胶质细胞中的主要亚型。在人和豚鼠中，胶质细胞也表达PKCβI。黏膜中的梭形细胞对PKCα和PKCγ有免疫反应，在肌肉层中，类似的细胞有PKCγ免疫反应性和PKCθ免疫反应性。这些梭形细胞在形态上与 Cajal 间质细胞相似。蛋白质免疫印迹分析和逆转录聚合酶链反应证实了组织中PKC亚型蛋白和mRNA的存在。我们得出结论，在人体组织的肠神经元和肠肌中存在不同PKC的细胞类型特异性表达，并且实验动物和人类之间的表达模式有很强 的相似性，但也观察到一些明显的差异。
