Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes.
Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes.
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DOI：
10.1038/s41419-017-0171-8
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发表时间：
2018-02-19
影响因子：
9
通讯作者：
Ju WK
中科院分区：
文献类型：
--
作者：
Shim MS;Kim KY;Bu JH;Nam HS;Jeong SW;Park TL;Ellisman MH;Weinreb RN;Ju WK
Glaucoma is characterized by a progressive loss of retinal ganglion cells and their axons, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role. However, whether the activation of cyclic adenosine 3′,5′-monophosphate (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell death via the AKT/Bim/Bax signaling pathway. Furthermore, elevated intracellular cAMP exacerbates vulnerability to oxidative stress in ONH astrocytes, and this may contribute to axonal damage in glaucomatous neurodegeneration. Inhibition of intracellular cAMP/PKA signaling activation protects ONH astrocytes by increasing AKT phosphorylation against oxidative stress. These results strongly indicate that activation of cAMP/PKA pathway has an important role in astrocyte dysfunction, and suggest that modulating cAMP/PKA pathway has therapeutic potential for glaucomatous ONH degeneration.
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