Ardaillou R, Stefanovic V, Dussaule J C, Ardaillou N
INSERM 64, Hôpital Tenon, Paris.
C R Seances Soc Biol Fil. 1992;186(6):626-34.
The ectoenzymes acting in the metabolism of peptides play an essential role in renal cell-cell communication. We have studied four of these ectoenzymes, aminopeptidases N and A (APN, APA), dipeptidylpeptidase IV (DPP IV) and neutral endopeptidase (NEP) in cultured human glomerular mesangial and epithelial cells and cultured rabbit renal cortical vascular smooth muscle cells. APN is present at the surface of both mesangial and epithelial cells with identical characteristics. Its expression (enzyme activity and immunoreactive protein) is induced by phorbol-esters and other protein kinase C-stimulating agents. APA is present only in glomerular epithelial cells. Its expression is induced by glucocorticoids and cyclic AMP-stimulating agents. DPP IV is also present only in glomerular epithelial cells. Its expression (enzyme activity, immunoreactive protein and mRNA) is induced by interferon gamma. NEP is present in glomerular epithelial cells and vascular smooth muscle cells. The expression of the latter enzyme is inhibited in the presence of serum via the combined effect of Ca2+i and PKC-stimulating agents. In contrast, glucocorticoids and cyclic GMP induce its expression. NEP plays a major role in the catabolism by these cells of atrial natriuretic factor. All these data emphasize the multiplicity of the mechanisms controlling ectopeptidase expression in cultured glomerular and renal vascular cells.
作用于肽代谢的外切酶在肾细胞间通讯中起重要作用。我们在培养的人肾小球系膜细胞和上皮细胞以及培养的兔肾皮质血管平滑肌细胞中研究了其中四种外切酶,即氨肽酶N和A(APN、APA)、二肽基肽酶IV(DPP IV)和中性内肽酶(NEP)。APN以相同的特性存在于系膜细胞和上皮细胞表面。其表达(酶活性和免疫反应性蛋白)由佛波酯和其他蛋白激酶C刺激剂诱导。APA仅存在于肾小球上皮细胞中。其表达由糖皮质激素和环磷酸腺苷刺激剂诱导。DPP IV也仅存在于肾小球上皮细胞中。其表达(酶活性、免疫反应性蛋白和mRNA)由干扰素γ诱导。NEP存在于肾小球上皮细胞和血管平滑肌细胞中。在血清存在的情况下,通过Ca2 + i和PKC刺激剂的联合作用,后一种酶的表达受到抑制。相反,糖皮质激素和环磷酸鸟苷诱导其表达。NEP在这些细胞对心房利钠因子的分解代谢中起主要作用。所有这些数据强调了控制培养的肾小球和肾血管细胞中外肽酶表达的机制的多样性。