Morita T, Ueki H, Kanagawa A
Second Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.
Cancer Lett. 1998 Jan 9;122(1-2):37-42. doi: 10.1016/s0304-3835(97)00362-5.
Although it is considered that the lipoprotein metabolism in tumor plays an important role in growth and multiplication, it is not clear as to the details. Lipoprotein lipase (LPL) is a key enzyme responsible for the hydrolysis of lipoprotein-triacylglyceride. In this study, we examined the regulatory step of LPL in lipoprotein metabolism of Ehrlich ascites tumor and especially the enzyme-release from the tumor cells. When LPL was stimulated to release from the tumor cells by the low molecular weight dextran sulfate (3.2 kDa), cyclic AMP content in the tumor cells was observed to increase rapidly in a time-dependent manner up to 30 s; its maximal effect was 1.5-fold higher than the basal level of cyclic AMP. The increase in cyclic AMP content was more enhanced in the presence of isobutylmethylxanthine and was never suppressed by propranolol. Moreover, cyclic AMP-dependent protein kinase (PKA) activity in the tumor cells was also recognized to elevate in a time- and dose-dependent manner. In addition, the release of LPL activity from the tumor cells was inhibited by 2',5'-dideoxyadenosine. These results suggest that LPL in the tumor cells is released through a pathway involving an activation of PKA associated with the rapid increase in cyclic AMP content.
尽管人们认为肿瘤中的脂蛋白代谢在生长和增殖中起重要作用，但具体细节尚不清楚。脂蛋白脂肪酶（LPL）是负责脂蛋白三酰甘油水解的关键酶。在本研究中，我们研究了艾氏腹水瘤脂蛋白代谢中LPL的调节步骤，特别是该酶从肿瘤细胞中的释放。当低分子量硫酸葡聚糖（3.2 kDa）刺激LPL从肿瘤细胞中释放时，观察到肿瘤细胞中的环磷酸腺苷（cAMP）含量在30 s内迅速以时间依赖性方式增加；其最大效应比cAMP的基础水平高1.5倍。在异丁基甲基黄嘌呤存在下，cAMP含量的增加更为明显，且不受普萘洛尔抑制。此外，肿瘤细胞中环磷酸腺苷依赖性蛋白激酶（PKA）的活性也被认为以时间和剂量依赖性方式升高。此外，2'，5'-二脱氧腺苷抑制了肿瘤细胞中LPL活性的释放。这些结果表明，肿瘤细胞中的LPL是通过一条涉及PKA激活并与cAMP含量快速增加相关的途径释放的。
