Lau P P, Palmer R L, Lambert H C, Song C S, Lutz F, Geokas M C
Department of Medicine, Veterans Administration Medical Center, Martinez, CA.
Biochem Biophys Res Commun. 1988 Apr 29;152(2):688-94. doi: 10.1016/s0006-291x(88)80093-7.
The action of Pseudomonas aeruginosa cytotoxin on isolated pancreatic acini was investigated. The release of amylase and serine protease zymogens from the isolated rat pancreatic acini was induced with increasing amounts of cytotoxin in vitro. The stimulated release of amylase reached 30% of total cellular content with 100 micrograms/mL of the purified cytotoxin. The induced release of amylase, trypsinogen, proelastase, and chymotrypsinogen reached the maximum after 75 minutes of incubation while lactate dehydrogenase began to appear after 15 minutes of incubation with a secondary biphasic increase at 75 min of incubation. The concentrations of acinar mRNAs of amylase, trypsinogen, proelastase, and chymotrypsinogen, as measured by dot-blot hybridization with the cloned cDNAs of amylase, trypsinogen I, proelastase II, and chymotrypsinogen B of the rat, decreased with time and were significantly lower than in the untreated acini. It is concluded that cytotoxin stimulates the release of amylase and protease zymogens with a concomitant increase in membrane permeability and a decrease of cellular mRNA levels. The inhibition of gene expression is attributable merely to a generalized toxic effect upon cellular metabolism.
研究了铜绿假单胞菌细胞毒素对分离的胰腺腺泡的作用。在体外，随着细胞毒素量的增加，分离的大鼠胰腺腺泡中淀粉酶和丝氨酸蛋白酶原的释放被诱导。用100微克/毫升的纯化细胞毒素时，淀粉酶的刺激释放量达到细胞总含量的30%。淀粉酶、胰蛋白酶原、弹性蛋白酶原和糜蛋白酶原的诱导释放量在孵育75分钟后达到最大值，而乳酸脱氢酶在孵育15分钟后开始出现，并在孵育75分钟时出现二次双相增加。通过与大鼠淀粉酶、胰蛋白酶原I、弹性蛋白酶原II和糜蛋白酶原B的克隆cDNA进行点杂交测定，淀粉酶、胰蛋白酶原、弹性蛋白酶原和糜蛋白酶原的腺泡mRNA浓度随时间下降，且显著低于未处理的腺泡。结论是，细胞毒素刺激淀粉酶和蛋白酶原的释放，同时膜通透性增加，细胞mRNA水平降低。基因表达的抑制仅仅归因于对细胞代谢的普遍毒性作用。
