Alpha-melanocyte stimulating hormone (α-MSH) is a post-caspase suppressor of apoptosis in RAW 264.7 macrophages.
Alpha-melanocyte stimulating hormone (α-MSH) is a post-caspase suppressor of apoptosis in RAW 264.7 macrophages.
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DOI：
10.1371/journal.pone.0074488
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Taylor AW
中科院分区：
文献类型：
--
作者：
Taylor AW
神经肽α-黑素细胞刺激激素（α-MSH）是免疫抑制眼部微环境中免疫细胞活性的重要调节剂。它的组成性存在不仅抑制巨噬细胞炎症活性，还参与视网膜色素上皮细胞（RPE）介导的巨噬细胞激活，其功能类似于骨髓抑制细胞。此外，α-MSH 促进替代激活的巨噬细胞的存活，而没有 α-MSH RPE 会诱导巨噬细胞凋亡，这被视为 TUNEL 染色细胞增加。由于对 α-MSH 作为抗凋亡因子知之甚少，因此在引发细胞凋亡的血清饥饿条件下，在 RAW 264.7 巨噬细胞中检查了 α-MSH 对 caspase 活性、线粒体膜电位、Bcl2 至 BAX 表达、TUNEL 染色和膜联蛋白 V 结合的影响。 α-MSH 对激活的 Caspase 9 和 Caspase 3 没有影响，但抑制 Caspase 8 活性。此外，α-MSH不会提高线粒体膜电位，不会改变Bcl-2和BAX之间的比例，也不会减少Annexin V结合。这些结果表明，α-MSH 对 TUNEL 染色的减弱是通过 α-MSH 介导的凋亡途径的抑制，该途径位于 Caspase 3 之后但在 DNA 断裂之前。因此，当 α-MSH 促进巨噬细胞的替代激活时，它还提供生存信号，以及半胱天冬酶参与非凋亡活动的潜力，从而有助于形成免疫抑制微环境。
The neuropeptide alpha-melanocyte stimulating hormone (α-MSH) is an important regulator of immune cell activity within the immunosuppressive ocular microenvironment. Its constitutive presence not only suppresses macrophage inflammatory activity, it also participates in retinal pigment epithelial cell (RPE) mediated activation of macrophages to function similar to myeloid suppressor cells. In addition, α-MSH promotes survival of the alternatively activated macrophages where without α-MSH RPE induce apoptosis in the macrophages, which is seen as increased TUNEL stained cells. Since there is little know about α-MSH as an anti-apoptotic factor, the effects of α-MSH on caspase activity, mitochondrial membrane potential, Bcl2 to BAX expression, along with TUNEL staining, and Annexin V binding were examined in RAW 264.7 macrophages under serum-starved conditions that trigger apoptosis. There was no effect of α-MSH on activated Caspase 9 and Caspase 3 while there was suppression of Caspase 8 activity. In addition, α-MSH did not improve mitochondrial membrane potential, change the ratio between Bcl-2 and BAX, nor reduce Annexin V binding. These results demonstrate that the diminution in TUNEL staining by α-MSH is through α-MSH mediating suppression of the apoptotic pathway that is post-Caspase 3, but before DNA fragmentation. Therefore, as α-MSH promotes the alternative activation of macrophages it also provides a survival signal, and the potential for the caspases to participate in non-apoptotic activities that can contribute to an immunosuppressive microenvironment.
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