H2S protects PC12 cells against toxicity of corticosterone by modulation of BDNF-TrkB pathway
H2S protects PC12 cells against toxicity of corticosterone by modulation of BDNF-TrkB pathway
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DOI：
10.1093/abbs/gmv098
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发表时间：
2015-11-01
影响因子：
3.7
通讯作者：
Tang, Xiaoqing
中科院分区：
文献类型：
--
作者：
Gao, Shenglan;Li, Wenting;Tang, Xiaoqing
皮质酮是糖皮质激素之一，对神经元具有毒性，在抑郁样行为和抑郁症中起重要作用。我们以前表明，硫化氢（H2S），一种新的生理介质，在抑郁症中起着抑制作用。然而，H2S触发的抗抑郁样作用的机制尚不清楚。脑源性神经营养因子（Brain-derived neurotrophic factor，BDNF）是一种神经营养因子，其神经保护作用是通过其高亲和力的原溶血素相关激酶B（Trk B）受体介导的。在这项研究中，探讨H2S诱导的抗抑郁样作用的潜在机制，我们探讨了H2S是否可以保护神经元免受皮质酮介导的细胞毒性，以及H2S的这种保护作用是否参与了BDNF-TrkB通路的调节。实验结果表明，硫氢化钠（NaHS）可抑制皮质酮诱导的PC 12细胞毒性、细胞凋亡、细胞内活性氧（ROS）的积累和线粒体膜电位（MMP）的降低。NaHS不仅诱导BDNF的上调，而且阻止皮质酮对BDNF的下调。用TrkB抑制剂K252 a阻断BDNF-TrkB通路后，H2S对皮质酮诱导的细胞毒性、细胞凋亡、ROS积累和MMP丢失的保护作用消失。这些结果表明，H2S通过调节BDNF-TrkB通路来保护皮质酮的神经毒性。
Corticosterone, one of the glucocorticoids, is toxic to neurons and plays an important role in depressive-like behavior and depression. We previously showed that hydrogen sulfide (H2S), a novel physiological mediator, plays an inhibitory role in depression. However, the mechanism underlying H2S-triggered antidepressant-like role is not clearly known. Brain-derived neurotrophic factor (BDNF), a neurotrophic factor, plays a neuroprotective role that is mediated by its high-affinity tropomysin-related kinase B (TrkB) receptor. In this study, to investigate the underlying mechanism of H2S-induced antidepressant-like role, we explored whether H2S could protect neurons against corticosterone-mediated cyctotoxicity and whether this protective role of H2S was involved in the regulation of BDNF-TrkB pathway. Our data demonstrated that sodium hydrosulfide (NaHS), the donor of H2S, could prevent corticosterone-induced cytotoxicity, apoptosis, accumulation of intracellular reactive oxygen species (ROS) and loss of mitochondrial membrane potential (MMP) in PC12 cells. NaHS not only induced the up-regulation of BDNF but also prevented the down-regulation of BDNF by corticosterone. It was also found that blocking BDNF-TrkB pathway by K252a, an inhibitor of TrkB, abolished the protection of H2S against corticosterone-induced cytotoxicity, apoptosis, accumulation of ROS, and loss of MMP. These results suggest that H2S protects against the neurotoxicity of corticosterone by modulation of the BDNF-TrkB pathway.