Neuroglobin (Ngb) is a new member of the globin family and a novel endogenous neuroprotective molecule, but its neuroprotective mechanisms remain largely undefined. Previous studies suggest Ngb is both physically and functionally related to mitochondria, however without direct evidence. Our recent discovery has shown that Ngb can physically interact with a number of mitochondrial proteins. In this study we aimed to define the physical interaction between Ngb and mitochondria by determining whether there is a mitochondrial distribution of Ngb under both physiological resting and pathological oxygen-glucose deprivation (OGD) conditions. Western blot for the first time revealed a small portion of Ngb was physically localized in mitochondria, and the relative mitochondrial Ngb level was significantly increased after OGD in primary cultured mouse cortical neurons, indicating a translocation of Ngb into mitochondria. Complementary approaches including confocal imaging and immuno-electron microscopy confirmed Ngb distribution in mitochondria under both basal resting condition and OGD. Inhibitors of mitochondria permeability transition pore (mPTP) and Voltage Dependent Anion Channel (VDAC) blocked OGD-induced increase of mitochondrial Ngb level, demonstrating a possible role of mPTP in Ngb’s mitochondrial translocation. We further found that Ngb overexpression-conferred neuroprotection was correlated with increased mitochondrial Ngb level, suggesting the mitochondria distribution of Ngb is clearly associated with and even might contribute to Ngb’s neuroprotection.
Our findings provide new insights that enhance the current knowledge of uveitis genetics by demonstrating the specific functional roles of IL1RAP and other IL-1 family genes in uveitis.
The flow-through blood supply improved pedicle perforator flap survival. Surgical relevance Perforator flap failure is mainly the result of impaired blood supply, as a flow-end blood configuration is nourished only by the perforator terminal branch of the artery. This work showed that the flow-through blood supply nourished by the perforator lateral branch improved flap survival, with dilatation of collateral vascular anastomoses and increased neoangiogenesis. The use of a flow-through configuration improves perforator flap survival and could therefore minimize morbidity resulting from flap necrosis.
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