A novel controllable hydrogen sulfide-releasing molecule protects human skin keratinocytes against methylglyoxal-induced injury and dysfunction.
A novel controllable hydrogen sulfide-releasing molecule protects human skin keratinocytes against methylglyoxal-induced injury and dysfunction.
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一种新型可控硫化氢释放分子可保护人类皮肤角质形成细胞免受甲基乙二醛引起的损伤和功能障碍。
DOI：
10.1159/000366339
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Zhang MF
中科院分区：
文献类型：
--
作者：
Yang CT;Zhao Y;Xian M;Li JH;Dong Q;Bai HB;Xu JD;Zhang MF
伤口愈合延迟是糖尿病常见的皮肤并发症，与角质形成细胞损伤和功能障碍有关。糖尿病皮肤组织和血浆中甲基乙二醛 (MGO)（一种 α-二羰基化合物）的水平升高，而硫化氢 (H2S)（一种关键的气体信号分子）的水平降低。有趣的是，在我们之前的研究中，这种气体显示出对皮肤的保护作用。迄今为止，没有证据表明 MGO 是否会影响角质形成细胞的活力和功能，或者 H2S 捐赠是否会消除这些影响并改善与 MGO 相关的伤口愈合损伤。目前的研究旨在检查 MGO 对人类皮肤角质形成细胞损伤和功能的影响，然后评估一种新型 H2S 释放分子的保护作用。合成了基于 N-巯基的 H2S 供体 (NSHD)-1，并分别在细胞培养基和细胞中观察了其释放 H2S 的能力。 HaCaT 细胞是人类皮肤角质形成细胞的一种细胞系，将其暴露于 MGO 中以建立体外糖尿病伤口愈合模型。在MGO暴露之前将NSHD-1添加到细胞中，观察到细胞活力、细胞凋亡、氧化应激、线粒体膜电位（MMP）和行为功能方面的细胞功能的改善。 MGO 治疗降低了 HaCaT 细胞的细胞活力，诱导细胞凋亡，增加细胞内活性氧 (ROS) 含量并抑制 MMP。该治疗还损害了细胞行为功能，其特征是细胞粘附和迁移减少。合成的 H2S 释放分子 NSHD-1 能够增加细胞培养基和细胞中的 H2S 水平。重要的是，用 NSHD-1 预处理可抑制 MGO 诱导的细胞活力和 MMP 降低、HaCaT 细胞中细胞凋亡和 ROS 积累的增加。预处理还能够改善粘附和迁移功能。这些结果表明，新型合成的 H2S 供体能够保护人类皮肤角质形成细胞免受 MGO 诱导的损伤和行为功能障碍。我们相信，未来更合理的H2S释放分子将为患有糖尿病伤口愈合延迟的患者带来缓解。
Delayed wound healing is a common skin complication of diabetes, which is associated with keratinocyte injury and dysfunction. Levels of methylglyoxal (MGO), an α-dicarbonyl compound, are elevated in diabetic skin tissue and plasma, while levels of hydrogen sulfide (H2S), a critical gaseous signaling molecule, are reduced. Interestingly, the gas has shown dermal protection in our previous study. To date, there is no evidence demonstrating whether MGO affects keratinocyte viability and function or H2S donation abolishes these effects and improves MGO-related impairment of wound healing. The current study was conducted to examine the effects of MGO on the injury and function in human skin keratinocytes and then to evaluate the protective action of a novel H2S-releasing molecule. An N-mercapto-based H2S donor (NSHD)-1 was synthesized and its ability to release H2S was observed in cell medium and cells, respectively. HaCaT cells, a cell line of human skin keratinocyte, were exposed to MGO to establish an in vitro diabetic wound healing model. NSHD-1 was added to the cells before MGO exposure and the improvement of cell function was observed in respect of cellular viability, apoptosis, oxidative stress, mitochondrial membrane potential (MMP) and behavioral function. Treatment with MGO decreased cell viability, induced cellular apoptosis, increased intracellular reactive oxygen species (ROS) content and depressed MMP in HaCaT cells. The treatment also damaged cell behavioral function, characterized by decreased cellular adhesion and migration. The synthesized H2S-releasing molecule, NSHD-1, was able to increase H2S levels in both cell medium and cells. Importantly, pretreatment with NSHD-1 inhibited MGO-induced decreases in cell viability and MMP, increases in apoptosis and ROS accumulation in HaCaT cells. The pretreatment was also able to improve adhesion and migration function. These results demonstrate that the novel synthesized H2S donor is able to protect human skin keratinocytes against MGO-induced injury and behavior dysfunction. We believe that more reasonable H2S-releasing molecules will bring relief to patients suffering from delayed wound healing in diabetes mellitus in the future.
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硫化氢通过恢复内皮祖细胞功能和激活 2 型糖尿病患者的血管生成素-1 来改善伤口愈合
影响因子：
7.7
作者：
Liu F;Chen DD;Sun X;Xie HH;Yuan H;Jia W;Chen AF
通讯作者：
Chen AF
DOI：
10.1016/s0006-291x(02)00576-4
发表时间：
2002-06-28
影响因子：
3.1
作者：
Bae, JS;Lee, SH;Kim, IS
通讯作者：
Kim, IS
DOI：
10.1016/j.bbrc.2004.06.011
发表时间：
2004-07-30
影响因子：
3.1
作者：
Fukunaga, M;Miyata, S;Kasuga, M
通讯作者：
Kasuga, M
影响因子：
4.3
作者：
Dong, Xiao-Bian;Yang, Chun-Tao;Liao, Xin-Xue
通讯作者：
Liao, Xin-Xue
影响因子：
9.8
作者：
Dhar, Arti;Desai, Kaushik;Wu, Lingyun
通讯作者：
Wu, Lingyun