New insights into mechanisms of gamma-diketone-induced axonopathy.
New insights into mechanisms of gamma-diketone-induced axonopathy.
复制标题
对γ-二酮诱导的轴突病机制的新见解。
DOI：
10.1007/s11064-009-9977-9
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发表时间：
2009
影响因子：
4.4
通讯作者：
Spencer,Peter
中科院分区：
文献类型：
--
作者：
Tshala-Katumbay,Desire;Desjardins,Paul;Sabri,Mohammad;Butterworth,Roger;Spencer,Peter
We analyzed the impact of axonopathy-inducing agents 1,2-diacetylbenzene (1,2-DAB) and 2,5-hexanedione (2,5-HD) on membrane-bound protein disulfide isomerase (mPDI) versus soluble PDI (sPDI), or PDI-family member thioredoxin (THX), and asked whether changes in PDI/THX were associated with production of oxidative/nitrosative species in the Sprague–Dawley rat. We show that 1,2-DAB and 2,5-HD lower the abundance of sPDI and THX. However, the protein expression of mPDI is increased in 1,2-DAB axonopathy and neuroproteins became moreS-nitrosylated. The abundance of heme oxygenase-1 (HO-1) and isoforms of nitric oxide synthase (neuronal, endothelial, and inducible NOS) remained unchanged suggesting thatS-nitrosylation occured via increased mPDI-transnitrosylation and/or diminished THX-denitrosylation. The transcription of PDI and glucose regulated protein-78 (GRP-78) remained unchanged indicating that post-translational modifications, e.g.S-nitrosylation, mediate the pathogenesis of γ-diketone axonopathy. These findings open opportunities for new therapeutic testing (e.g., supplementation with denitrosylating THX) in γ-diketone-induced axonal disease.
