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Different Mechanisms of Protective and Differentiative Activities of Homological Peptides TGENHR and TQVEHR

机译:同源肽TGENHR和TQVEHR的保护和分化活性的不同机制

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Previously we identified a six-membered fragment ~(354)TQVEHR~(359)of the C-terminal part of the PEDF(Pigment Epithelium-Derived Factor)differentiation factor molecule that shares homology with fragment ~(41)TGENHR~(46)of the HLDF(Human Leukemia Differentiation Factor)differentiation factor molecule,which is responsible for its differentiation activity.HLDF has been isolated from the culture medium of human promyelocytic leukemia cell line HL-60.Hexapeptides HLDF-6(TGENHR)and PEDF-6(TQVEHR)corresponding to these HLDF and PEDF molecule fragments,which were previously shown to induce cell differentiation(Kostanyan et al.(2000)Russian Journal of Bioorganic Chemistry,26,505-511),also have neuroprotective properties.Both peptides prevent degeneration of Purkinje cells of rat cerebellar vermis upon chemical hypoxia induced by sodium azide in vivo;this effect is also observed on a behavioral level.Peptide HLDF-6 but not PEDF-6 promotes survival of HL-60 cells upon chemical hypoxia.Peptides HLDF-6 and PEDF-6 affect different second messenger biosynthesis systems in HL-60 cells.HLDF-6 diminishes cyclic AMP level in those cells due to adenylate cyclase inhibition,while PEDF-6 inhibits phosphatidylinositol-specific phospholipase C stimulated by aluminum tetrafluoride anions.
机译:以前我们鉴定了PEDF(色素上皮衍生因子)分化因子分子C末端部分的六元片段〜(354)TQVEHR〜(359),与片段〜(41)TGENHR〜(46)具有同源性从人类早幼粒细胞白血病细胞系HL-60的培养基中分离出HLDF。六肽HLDF-6(TGENHR)和PEDF-6 (TQVEHR)与这些HLDF和PEDF分子片段相对应,这些片段先前已被证明可诱导细胞分化(Kostanyan等人(2000)Russian Journal of Bioorganic Chemistry,26,505-511),也具有神经保护特性。两种肽均可防止Purkinje变性叠氮化钠在体内对大鼠小脑ver细胞的化学缺氧作用;在行为水平上也观察到这种作用。肽HLDF-6而非PEDF-6促进化学缺氧时HL-60细胞的存活。 DF-6和PEDF-6影响HL-60细胞中不同的第二信使生物合成系统.HLDF-6由于抑制腺苷酸环化酶而降低了这些细胞中的环AMP含量,而PEDF-6抑制了四氟化铝阴离子刺激的磷脂酰肌醇特异性磷脂酶C. 。

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