Poly (ADP-Ribose) Transferase/Polymerase-1-Deficient Mice Resistant to Age-Dependent Decrease in β-Cell Proliferation
Poly (ADP-Ribose) Transferase/Polymerase-1-Deficient Mice Resistant to Age-Dependent Decrease in β-Cell Proliferation
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DOI：
10.2119/molmed.2011.00458
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发表时间：
2012-05-01
影响因子：
5.7
通讯作者：
Zhang, Ming-Xiang
中科院分区：
文献类型：
--
作者：
Gong, Lei;Liu, Fu-qiang;Zhang, Ming-Xiang
基础的和适应性的β细胞再生能力随着年龄的增长而下降，但潜在的分子机制仍然不完全清楚。多聚(二磷酸腺苷-核糖)聚合酶1(PARP-1)被认为是一种多功能酶和转录因子，调节胰岛β细胞死亡、再生和胰岛素分泌。我们分析了2月龄(幼龄)和12月龄(老年)野生型(WT)和PARP-1(-/-)小鼠在小剂量链脲佐菌素(STZ)治疗前后的β细胞再生能力，以及β细胞再生的刺激和潜在机制。在注射STZ之前，年轻的WT和PARP-1(-/-)小鼠表现出类似的β细胞增殖。相比之下，老年WT而不是老年PARP-1(-/-)小鼠表现出严格限制的β细胞增殖。在进一步评估随年龄增长的适应性β细胞再生能力时，我们观察到，使用单一低剂量的STZ，年轻WT小鼠和PARP-1小鼠表现出类似的β细胞增殖增加，而老年WT小鼠几乎没有变化。令人惊讶的是，给予STZ后，老年PARP-1(-/-)小鼠的适应性β细胞增殖能力显著高于老年WT小鼠。β细胞团的扩张能力与再生(REG)基因RegI和RegII水平的增加有关，但与RegIV无关。因此，随着年龄的增长，PARP-1(-/-)是小鼠β细胞再生的关键调节因子。在线地址：http://www.molmed.org doi：10.2119/molmed.2011.00458
Basal and adaptive beta-cell regeneration capacity declines with old age, but the underlying molecular mechanisms remain incompletely understood. Poly (adenosine diphosphate (ADP)-ribose) polymerase 1 (PARP-1) is considered a multifunctional enzyme and transcription factor that regulates pancreatic beta-cell death, regeneration and insulin secretion. We analyzed the capacity of beta-cell regeneration in 2-month-old (young) and 12-month-old (old) wild-type (WT) and PARP-1(-/-) mice before and after low-dose streptozotocin (STZ), a stimulus of beta-cell regeneration and the underlying mechanism. Before STZ administration, young WT and PARP-1(-/-) mice showed similar beta-cell proliferation. By contrast, old WT but not old PARP-1(-/-) mice showed severely restricted beta-cell proliferation. In further assessment of the adaptive beta-cell regeneration capacity with age, we observed that with a single low dose of STZ, young WT and PARP-1 mice showed a similar increase in beta-cell proliferation, with few changes in old WT mice. Surprisingly, adaptive beta-cell proliferation capacity was significantly higher in old PARP-1(-/-) mice than old WT mice after STZ administration. The ability of beta-cell mass to expand was associated with increased levels of the regenerating (Reg) genes RegI and RegII but not RegIV. Therefore, PARP-1(-/-) is a key regulator in beta-cell regeneration with advancing age in mice. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00458