Distribution and neurochemical characterization of protein kinase C-theta and -delta in the rodent hypothalamus.

Distribution and neurochemical characterization of protein kinase C-theta and -delta in the rodent hypothalamus.
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DOI:
10.1016/j.neuroscience.2010.07.064
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发表时间:
2010-11-10
期刊:
影响因子:
3.3
通讯作者:
Clegg, D. J.
Clegg, D. J.
中科院分区:
医学3区
文献类型:
--
作者:
Irani, B. G.;Donato, J., Jr.;Olson, D. P.;Lowell, B. B.;Sacktor, T. C.;Reyland, M. E.;Tolson, K. P.;Zinn, A. R.;Ueta, Y.;Sakata, I.;Zigman, J. M.;Elias, C. F.;Clegg, D. J.

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PKC-theta(PKC-θ)是一种新的蛋白激酶C家族成员,在外周调节多种功能。然而,它在中南欧的存在和作用在很大程度上仍不为人所知。最近,我们证实了下丘脑弓状核(Arc)中PKC-θ的存在以及弓状核抑制饮食诱导肥胖小鼠的PKC-θ。NPKC组的另一种亚型PKC-δ在包括丘脑和海马区在内的几个非下丘脑区表达。尽管PKC-δ参与调节下丘脑葡萄糖稳态,但其在下丘脑中的分布此前尚未被描述。在本研究中,我们用免疫组织化学方法检测了PKC-θ和-δ在大鼠和小鼠下丘脑中的分布。在下丘脑弓状核、下丘脑外侧区、穹隆周围区和结节乳头核中发现了PKC-θ免疫反应阳性神经元。PKC-δ免疫反应阳性神经元见于室旁核和视上核。对表达绿色荧光蛋白的小鼠的双标免疫组织化学研究表明,pKC-θ在下丘脑外侧瘦素受体(Lepr-b)神经元中高度共存,而在下丘脑外侧Lepr-b神经元中不表达。在催产素增强的黄色荧光蛋白小鼠和精氨酸加压素增强的绿色荧光蛋白转基因大鼠的双标记免疫组织化学中,PKC-δ在脑室旁和视上催产素能神经元中高度共存,而在加压素能神经元中不表达。我们认为,PKC-θ和-δ在不同的下丘脑神经元群中都有表达。
PKC-theta (PKC-θ), a member of the novel protein kinase C family (nPKC), regulates a wide variety of functions in the periphery. However, its presence and role in the CNS has remained largely unknown. Recently, we demonstrated the presence of PKC-θ in the arcuate hypothalamic nucleus (ARC) and knockdown of PKC-θ from the ARC protected mice from developing diet-induced obesity. Another isoform of the nPKC group, PKC-delta (PKC-δ), is expressed in several non-hypothalamic brain sites including the thalamus and hippocampus. Although PKC-δ has been implicated in regulating hypothalamic glucose homeostasis, its distribution in the hypothalamus has not previously been described. In the current study, we used immunohistochemistry to examine the distribution of PKC-θ and -δ immunoreactivity in rat and mouse hypothalamus. We found PKC-θ immunoreactive neurons in several hypothalamic nuclei including the ARC, lateral hypothalamic area, perifornical area and tuberomammillary nucleus. PKC-δ immunoreactive neurons were found in the paraventricular and supraoptic nuclei. Double-label immunohistochemisty in mice expressing green fluorescent protein either with the long form of leptin receptor (LepR-b) or in orexin (ORX) neurons indicated that PKC-θ is highly colocalized in lateral hypothalamic ORX neurons but not in lateral hypothalamic LepR-b neurons. Double-label immunohistochemistry in oxytocin-enhanced yellow fluorescent protein mice or arginine vasopressin-enhanced green fluorescent protein (AVP-EGFP) transgenic rats revealed a high degree of colocalization of PKC-δ within paraventricular and supraoptic oxytocin neurons but not the vasopressinergic neurons. We conclude that PKC-θ and -δ are expressed in different hypothalamic neuronal populations.
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发表时间: 2000-12-22
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