Parfenova H, Eidson T H, Leffler C W
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
Am J Physiol. 1997 Jul;273(1 Pt 1):C277-88. doi: 10.1152/ajpcell.1997.273.1.C277.
Cyclooxygenase (COX) isoform expression, intracellular localization, and function in endothelial cells from the newborn pig cerebral microvessels were investigated using COX-1- and COX-2-specific antibodies and the COX-2 inhibitor NS-398. Cerebral microvessels, microvascular endothelium, and cultured endothelial cells constitutively express both COX-1 and COX-2. NS-398 inhibits 70-90% of endothelial prostanoid production. Endothelial cells grown in noncontact coculture with smooth muscle cells for 24-48 h demonstrate a stable induction of COX-2 protein and an NS-398-sensitive increase in prostanoid synthesis. The induction of endothelial COX in mixed cell coculture is accompanied by intracellular redistribution of COX-2. In cocultured endothelial cells, COX-2 is observed in the nucleus, nuclear envelope, and cytoplasm, compared with the mainly intranuclear localization of COX-2 in cells cultured separately. No changes were observed in COX-1 protein, localized in endothelial cell cytoplasm and the nuclear envelope. These results indicate that smooth muscle cells may modify endothelial function by upregulating COX-2, which is a major functional COX isoform in cerebral microvascular endothelial cells.
利用COX - 1和COX - 2特异性抗体以及COX - 2抑制剂NS - 398，研究了新生猪脑微血管内皮细胞中环氧合酶（COX）同工型的表达、细胞内定位及其功能。脑微血管、微血管内皮细胞和培养的内皮细胞组成性地表达COX - 1和COX - 2。NS - 398可抑制70 - 90%的内皮前列腺素生成。与平滑肌细胞进行非接触共培养24 - 48小时的内皮细胞显示出COX - 2蛋白的稳定诱导以及前列腺素合成中对NS - 398敏感的增加。混合细胞共培养中内皮COX的诱导伴随着COX - 2的细胞内重新分布。在共培养的内皮细胞中，与单独培养的细胞中COX - 2主要定位于细胞核内相比，在细胞核、核膜和细胞质中均观察到COX - 2。定位于内皮细胞质和核膜的COX - 1蛋白未观察到变化。这些结果表明，平滑肌细胞可能通过上调COX - 2来改变内皮功能，而COX - 2是脑微血管内皮细胞中的主要功能性COX同工型。
