Rami J, Stenzel W, Sasic S M, Puel-M'Rini C, Besombes J P, Elias J A, Rooney S A
Institut National de la Santé et de la Recherche Medicale, Faculté de Médecine de Toulouse, Université Paul Sabatier, Toulouse, France.
Am J Physiol. 1994 Aug;267(2 Pt 1):L128-36. doi: 10.1152/ajplung.1994.267.2.L128.
Silica instillation causes a massive increase in lung surfactant. Two populations of type II pneumocytes can be isolated from rats administered silica by intratracheal injection: type IIA cells similar to type II cells from normal rats and type IIB cells, which are larger and contain elevated levels of surfactant protein A and phospholipid. Activities of choline-phosphate cytidylyltransferase, a rate-regulatory enzyme in phosphatidylcholine biosynthesis, and fatty-acid synthase (FAS) are increased in type IIB cells isolated from rats 14 days after silica injection. In the present study, we examined the increase in FAS and cytidylyltransferase activities in type IIB cells as a function of time after silica administration. FAS activity increased rapidly, was approximately threefold elevated 1 day after silica administration and has reached close to the maximum increase by 3 days. Cytidylyltransferase activity was not increased on day 1, was significantly increased on day 3 but was not maximally increased until day 7. Inhibition of de novo fatty-acid biosynthesis, by in vivo injection of hydroxycitric acid and inclusion of agaric acid in the type II cell culture medium, abolished the increase in cytidylyltransferase activity on day 3 but not FAS and had no effect on activities of two other enzymes of phospholipid synthesis. FAS mRNA levels were not increased in type IIB cells isolated 1-14 days after silica injection. These data show that the increase in FAS activity in type IIB cells is an early response to silica, that it mediates the increase in cytidylyltransferase activity, and that it is not due to enhanced FAS gene expression.
注入二氧化硅会导致肺表面活性物质大量增加。通过气管内注射给予二氧化硅的大鼠体内可分离出两类II型肺细胞：类似于正常大鼠II型细胞的IIA型细胞和体积较大、表面活性蛋白A和磷脂水平升高的IIB型细胞。在二氧化硅注射14天后从大鼠分离出的IIB型细胞中，磷脂酰胆碱生物合成中的限速酶胆碱磷酸胞苷转移酶和脂肪酸合酶（FAS）的活性增加。在本研究中，我们研究了二氧化硅给药后IIB型细胞中FAS和胞苷转移酶活性随时间的增加情况。FAS活性迅速增加，在二氧化硅给药1天后升高约三倍，并在3天时接近最大增幅。胞苷转移酶活性在第1天没有增加，在第3天显著增加，但直到第7天才达到最大增幅。通过体内注射羟基柠檬酸以及在II型细胞培养基中加入木耳酸抑制脂肪酸从头生物合成，消除了第3天胞苷转移酶活性的增加，但对FAS没有影响，且对磷脂合成的另外两种酶的活性也没有影响。在二氧化硅注射后1 - 14天分离出的IIB型细胞中，FAS mRNA水平没有增加。这些数据表明，IIB型细胞中FAS活性的增加是对二氧化硅的早期反应，它介导了胞苷转移酶活性的增加，且这并非由于FAS基因表达增强所致。
