The beta isoforms of protein Kinase C (PKC) are closely involved in the regulation of cell protein transport and secretion. We have shown in different cellular types that treatment with HNE in a concentration range detectable in many pathophysiological conditions is able to induce selective activation of betaPKCs through direct interaction between the aldehyde and these isoenzymes. In isolated rat hepatocytes this specific isoenzyme activation plays a key role in the transport of procathepsin D from the trans-Golgi network to the endosomal-lysosomal compartment and in the exocytosis of mature cathepsin D. In NT2 neurons, HNE-mediated betaPKC activation induces an increase in intracellular amyloid beta production, without affecting full-length amyloid precursor protein expression. In a mouse macrophage-like cell line, the same beta isoform activation increases the release of the MCP-1 chemokine. Thus, pathophysiological HNE concentrations (0.1-1 microM) derived from a slight imbalance of the redox state are able to alter protein trafficking through beta PKC activation. These results suggest that mild oxidative stress and the PKC signal transduction pathway are closely involved in the pathophysiology of many diseases caused by changes in protein trafficking and release.

中文翻译：

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PKC依赖性途径在HNE诱导的细胞蛋白转运和分泌中的作用。

蛋白激酶C（PKC）的β亚型与细胞蛋白转运和分泌的调节密切相关。我们已经在不同的细胞类型中表明，在许多病理生理条件下可检测到的浓度范围内用HNE进行处理，能够通过醛与这些同工酶之间的直接相互作用来诱导betaPKC的选择性激活。在分离的大鼠肝细胞中，这种特定的同工酶激活在组织蛋白酶D从反高尔基体网络向内体溶酶体区室的运输以及成熟组织蛋白酶D的胞吐作用中起着关键作用。在NT2神经元中，HNE介导的betaPKC激活诱导了增加细胞内淀粉样蛋白β的产量，而不会影响全长淀粉样蛋白前体蛋白的表达。在小鼠巨噬细胞样细胞系中，相同的β亚型激活会增加MCP-1趋化因子的释放。因此，由氧化还原状态的轻微失衡引起的病理生理学HNE浓度（0.1-1 microM）能够通过βPKC激活来改变蛋白质运输。这些结果表明，轻度的氧化应激和PKC信号转导途径与蛋白质运输和释放变化引起的许多疾病的病理生理密切相关。