Vitiligo: a possible model of degenerative diseases.
Vitiligo: a possible model of degenerative diseases.
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DOI：
10.1371/journal.pone.0059782
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Picardo M
中科院分区：
文献类型：
--
作者：
Bellei B;Pitisci A;Ottaviani M;Ludovici M;Cota C;Luzi F;Dell'Anna ML;Picardo M
白癜风的特征是皮肤和毛囊中的色素细胞逐渐消失。一些体外和体内研究表明，白癜风的氧化还原状态发生了改变，提示细胞氧化还原平衡的丧失可能是白癜风的致病机制。然而，尽管有大量的数据支持氧化应激的致病作用，但对于氧化应激导致的黑素细胞从表皮消失的原因，仍然没有达成共识的解释。在这项研究中，体外培养的非皮损性白癜风皮肤黑素细胞的特征揭示了神经退行性疾病常见的信号转导通路在细胞水平上的异常功能，包括脂质代谢的改变，丝裂原激活的蛋白激酶(MAPK)和cAMP反应元件结合蛋白(CREB)的过度激活，结构性的P53依赖的应激信号转导通路，以及对促凋亡刺激的敏感性增强。值得注意的是，亚细胞毒性氧化应激的这些长期影响也是衰老前细胞表型的生物标志物。与此一致的是，白癜风细胞显示p16显著增加，与捐赠者的实际年龄无关。此外，白癜风黑素细胞在衰老相关分泌表型(SAPS)中产生了许多生物活性蛋白，如白介素6(IL-6)、基质金属蛋白酶-3(MMP3)、环氧合酶-2(COX-2)、胰岛素样生长因子结合蛋白-3和7(IGFBP3、IGFBP7)。总而言之，这些数据证明了黑素细胞退行性变背后的一个复杂的病理生理学谜题，从生物学的角度来看，类似于神经退行性疾病。我们的结果提示了新的可能的干预靶点，结合目前的治疗方法可以纠正黑素细胞的内在缺陷。
Vitiligo is characterized by the progressive disappearance of pigment cells from skin and hair follicle. Several in vitro and in vivo studies show evidence of an altered redox status, suggesting that loss of cellular redox equilibrium might be the pathogenic mechanism in vitiligo. However, despite the numerous data supporting a pathogenic role of oxidative stress, there is still no consensus explanation underlying the oxidative stress-driven disappear of melanocytes from the epidermis. In this study, in vitro characterization of melanocytes cultures from non-lesional vitiligo skin revealed at the cellular level aberrant function of signal transduction pathways common with neurodegenerative diseases including modification of lipid metabolism, hyperactivation of mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB), constitutive p53-dependent stress signal transduction cascades, and enhanced sensibility to pro-apoptotic stimuli. Notably, these long-term effects of subcytotoxic oxidative stress are also biomarkers of pre-senescent cellular phenotype. Consistent with this, vitiligo cells showed a significant increase in p16 that did not correlate with the chronological age of the donor. Moreover, vitiligo melanocytes produced many biologically active proteins among the senescence-associated secretory phenotype (SAPS), such as interleukin-6 (IL-6), matrix metallo proteinase-3 (MMP3), cyclooxygenase-2 (Cox-2), insulin-like growth factor-binding protein-3 and 7 (IGFBP3, IGFBP7). Together, these data argue for a complicated pathophysiologic puzzle underlying melanocytes degeneration resembling, from the biological point of view, neurodegenerative diseases. Our results suggest new possible targets for intervention that in combination with current therapies could correct melanocytes intrinsic defects.
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DOI：
10.18632/aging.100281
发表时间：
2011-02
期刊：
Aging
影响因子：
--
作者：
Blagosklonny MV
通讯作者：
Blagosklonny MV
影响因子：
4.8
作者：
Bedogni, B;Pani, G;Galeotti, T
通讯作者：
Galeotti, T
DOI：
10.1111/j.1600-0749.2007.00385.x
发表时间：
2007-08-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Bondanza, Sergio;Maurelli, Riccardo;Guerra, Liliana
通讯作者：
Guerra, Liliana
影响因子：
7.8
作者：
Gamba, Paola;Leonarduzzi, Gabriella;Poli, Giuseppe
通讯作者：
Poli, Giuseppe
由组织化学，放射自显微镜和电子显微镜研究确定的非肿瘤性黑素细胞的有丝分裂活性。
DOI：
10.1083/jcb.66.3.663
发表时间：
1975-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jimbow K;Roth SI;Fitzpatrick TB;Szabo G
通讯作者：
Szabo G