Zn2+ inhibits nitric oxide formation in response to lipopolysaccharides:: Implication in its anti-inflammatory activity
Zn2+ inhibits nitric oxide formation in response to lipopolysaccharides:: Implication in its anti-inflammatory activity
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DOI：
10.1016/s0014-2999(97)01416-7
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发表时间：
1998-01-12
影响因子：
5
通讯作者：
Caldwell, RW
中科院分区：
文献类型：
--
作者：
Abou-Mohamed, G;Papapetropoulos, A;Caldwell, RW
有令人信服的证据表明Zn 2+具有抗炎作用。大多数炎性疾病与诱导型一氧化氮（NO）合酶的增加有关。此外，炎症介质如组胺或缓激肽刺激组成型NO合酶。因此，进行本研究以研究Zn 2+是否抑制诱导型NO合酶的产生和/或组成型NO合酶活性以产生NO。给予缺锌（ZD）大鼠、补充硫酸锌（ZG）的大鼠，皮下注射10 mg/kg，或对照组导致其血清Zn 2+显著降低。从ZD或ZG分离的大鼠血浆中N-G-硝基-L-精氨酸甲酯（L-NAME）敏感的环GMP（cGMP）水平显著低于从对照动物获得的水平。锌（100-150 μ M）产生的剂量依赖性抑制脂多糖或白细胞介素-1 β诱导的NO形成在离体大鼠主动脉平滑肌细胞。环己脲或放线菌素D相比，由150 μ M Zn 2+抑制NO形成的时间过程并不表明Zn 2+对诱导型NO合酶蛋白合成的影响。此外，Zn 2+（150 μ M）显著降低脂多糖处理大鼠肺匀浆中[H-3]精氨酸转化为[H-3]瓜氨酸的速率。孵育大鼠主动脉平滑肌细胞和牛肺动脉内皮细胞共培养物与Zn 2+（150 μ M）引起的基础和缓激肽或A-23187诱导的cGMP的形成显着减少。因此，我们的研究结果表明，锌是能够抑制脂多糖或白细胞介素-1 β诱导的NO的形成，以及NO形成的组成型NO合酶的基础上或响应缓激肽或A-23187，并可能解释报道的抗炎活性的锌。(C)1998年Elsevier Science B.V.
There is compelling evidence to indicate an anti-inflammatory action of Zn2+. Most inflammatory diseases are associated with an increase of the inducible form of nitric oxide (NO) synthase. Additionally, inflammatory mediators such as histamine or bradykinin stimulate the constitutive NO synthase. Thus, the present study was undertaken to investigate whether Zn2+ inhibits production of inducible NO synthase and/or constitutive NO synthase activity to produce NO. Lipopolysaccharide, 5 mg/kg i.v., administered to Zn2+-deficient (ZD) rats, rats supplemented with Zn2+ sulfate(ZG), 10 mg/kg s.c., or controls resulted in a significant reduction of their serum Zn2+. The levels of N-G-nitro-L-arginine methylester (L-NAME)-sensitive cyclic GMP (cGMP) in aortas isolated from ZD or ZG were significantly lower than those obtained from control animals. Zinc (100-150 mu M) produced a dose-dependent inhibition of lipopolysaccharide or interleukin-1 beta-induced NO formation in isolated rat aortic smooth muscle cells. Compared to cyclohexamide or actinomycin-D, the time course of inhibition of NO formation by 150 mu M Zn2+ did not suggest an effect of Zn2+ on inducible NO synthase protein synthesis. Moreover, Zn2+ (150 mu M) significantly reduced the rate of conversion of [H-3]arginine to [H-3]citrulline in lung homogenates from lipopolysaccharide-treated rats. Incubation of rat aortic smooth muscle cells and bovine pulmonary artery endothelial cell co-cultures with Zn2+ (150 mu M) caused a significant reduction in basal and bradykinin-or A-23187-induced formation of cGMP. Thus, our results indicate that Zn2+ is capable of inhibiting lipopolysaccharide-or interleukin-1 beta-induced NO formation as well as NO formation by constitutive NO synthase basally or in response to bradykinin or A-23187, and may explain the reported anti-inflammatory activity of Zn2+. (C) 1998 Elsevier Science B.V.