Regulation of cell growth and brain function by polyamines

1.我们以前曾报道过，在大肠杆菌中，多胺在翻译水平上刺激了对细胞生长至关重要的特定蛋白质的合成，如OPPA、CyA和Rpos(σ^&lt；38&gt；)。我们发现，多胺也在翻译水平上刺激了FECI和FIS的合成。FECI和FIS促进与铁吸收和能量代谢有关的mRNAs的表达，以及rRNA和一些tRNAs的表达。它们的mRNAs的Shine-Dalgarno(SD)序列没有位于通常的位置。当SD序列在这些mRNA上的正常位置被创建时，蛋白质的合成不再受到多胺的影响。因此，这些mRNAs的共同特征是具有弱的SD序列。我们认为在翻译水平上被多胺增强表达的一组基因被称为“多胺调节子”。摘要研究了不同的蒽醌多胺对非洲爪哇…细胞表达的N-甲基-D-天冬氨酸受体的影响。更多的Aevis卵母细胞。在电压钳制为-70 mV时，所有水通道蛋白衍生物均抑制卵母细胞的受体反应，其IC_(50)值在4~22μM之间。AQ亚精胺(AQ34)抑制NR1/NR2受体的反应，但不抑制AMPA受体的反应，提示AQ34是NMDA的选择性拮抗剂。使用突变的NR1和NR2亚基的实验结果确定了影响AQ34阻断的残基。这些残基位于选择性过滤器/通道最窄狭窄处的外前庭和选择性过滤器水平以下的内前庭。卒中患者血浆中乙酰多胺氧化酶(AcPAO)、精胺氧化酶(SMO)和丙烯醛水平显著升高。卒中大小与丙烯醛和总多胺氧化酶(AcPAO+SMO)的乘积接近平行。卒中发病后，AcPAO首先升高，然后是SMO升高，最后是丙烯醛。1例MRI或CT发现局灶性损害前，AcPAO和SMO升高。此外，在一些症状轻微的患者(11例)中，MRI证实了中风，这些患者的总多胺氧化酶和丙烯醛水平升高。结果表明，AcPAO、SMO和丙烯醛是较好的卒中标志物。较少

1. We have reported previously that the synthesis of specific proteins such as OppA, Cya and RpoS (σ^<38>), which are important for cell growth, is stimulated by polyamines at the level of translation in E.coli. We found that the synthesis of FecI and Fis was also stimulated by polyamines at the level of translation. The FecI and Fis enhance expression of mRNAs that are involved in iron uptake and energy metabolism, and of rRNA and some tRNAs. The Shine-Dalgarno (SD) sequence of their mRNAs was not located at the usual position. When the SD sequences were created at the normal position on these mRNAs, protein synthesis was no longer influenced by polyamines. Thus, the common characteristic of these mRNAs was to have a weak SD sequence. We propose that a group of genes whose expression is enhanced by polyamines at the level of translation is referred to as a "polyamine modulon".2. The effects of various anthraquinone polyamines (AQP) were studied at NMDA receptors expressed in Xenopus l … More aevis oocytes. All AQP derivatives inhibited responses of NR1/NR2 receptors in oocytes voltage-clamped at -70mV, with IC_<50> values between 4 and 22μM. The block was strongly voltage-dependent. AQ spermidine (AQ34) inhibited responses of NR1/NR2 receptors but did not inhibit responses of AMPA receptors indicating that AQ34 is preferential NMDA antagonists. Results of experiments using mutant NR1 and NR2 subunits identified residues that influence block by AQ34. These residues are located in the outer vestibule at the selectivity filter/narrowest constriction of the channel and in the inner vestibule below the level of the selectivity filter.3. The levels of acetylpolyamine oxidase (AcPAO), spermine oxidase (SMO), and acrolein were significantly increased in the plasma of stroke patients. The size of stroke was nearly parallel with the multiplied value of acrolein and total polyamine oxidase (AcPAO plus SMO). After the onset of stroke, an increase in AcPAO first occurred, followed by increased level of SMO and finally acrolein. In 1 case, an increase in AcPAO and SMO preceded focal damage as detected by MRI or CT. Furthermore, stroke was confirmed by MRI in a number of mildly symptomatic patients (11 cases) who had increased levels of total polyamine oxidase and acrolein. The results indicate that AcPAO, SMO, and acrolein are good markers of stroke. Less