Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Mar 2020
Knockdown of macrophage migration inhibitory factor (MIF), a novel target to protect neurons from parthanatos induced by simulated post-spinal cord injury oxidative stress.
Parthanatos is a form of regulated cell death (RCD) that is closely linked to DNA damage, which is a common consequence of oxidative stress due to central nervous trauma, such as spinal cord injury (SCI). The mechanism by which apoptosis-inducing factor (AIF) mediates DNA strand breaks in parthanatos was not clear until the discovery of the nuclease function of MIF. A previous study suggested that observed results may not be reliable if the oxidative stress induced in cells observed under experimental pathological conditions does not accurately replicate the specific pathologies being studied. ⋯ The comet assay also displayed significantly fewer DNA strand breaks after MIF knockdown. This is the first study has verified that MIF knockdown enables to protect neurons from parthanatos under a simulated in vivo oxidative stress following SCI. It suggests that MIF knockdown is a promising therapy to rescue neurons suffering from oxidative stress-induced SCI pathology.
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Biochem. Biophys. Res. Commun. · Mar 2020
Suppression of miR-193a alleviates neuroinflammation and improves neurological function recovery after traumatic brain injury (TBI) in mice.
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the world, and is tightly associated with microglia-regulated neuroinflammation. However, the activation profile of microglia during the pathophysiological responses is still not fully understood. Micro-RNAs (miRs), as noncoding RNAs, are involved in the progression of TBI. ⋯ In contrast, LPS-induced activation of microglial cells and the expression of pro-inflammatory factors was markedly further accelerated by the transfection of miR-193a mimic. Taken together, TBI resulted in a robust neuroinflammatory response that was closely associated with the up-regulated miR-193a expression mainly in microglia/macrophages; however, miR-193a suppression significantly alleviated post-traumatic neuroinflammation and cognitive dysfunction. Therefore, miR-193a might be a promising therapeutic target for the treatment of TBI-associated neuroinflammation.
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Biochem. Biophys. Res. Commun. · Jan 2020
Sulfhydration of perilipin 1 is involved in the inhibitory effects of cystathionine gamma lyase/hydrogen sulfide on adipocyte lipolysis.
Hydrogen sulfide (H2S) is a novel adipokine mediating glucose uptake, lipid storage and mobilization, thus contributing to the genesis of obesity and associated diseases. Our previous work demonstrated that H2S inhibited isoproterenol-stimulated lipolysis by reducing the phosphorylation of perilipin 1 (plin-1), a lipid-droplet protein blocking lipase access. How H2S modulates plin-1 phosphorylation is still unclear. ⋯ Finally, plin-1 knockout abolished the effect of H2S on lipolysis, which indicates that plin-1 sulfhydration is a major direct target of H2S in lipolysis. We have identified a new post-translation modification, sulfhydration (direct action by H2S) of plin-1, causing reduced phosphorylation then decreased lipolysis. This finding also highlights a novel molecular regulatory mechanism of lipolysis.
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Biochem. Biophys. Res. Commun. · Nov 2019
Rosiglitazone ameliorates bile duct ligation-induced liver fibrosis by down-regulating NF-κB-TNF-α signaling pathway in a PPARγ-dependent manner.
Liver fibrosis is a major cause of morbidity and mortality worldwide. One of its therapeutic targets is peroxisome proliferator-activated receptor γ (PPARγ), with its ligands including rosiglitazone being tested in pre-clinical and clinical studies. However, the effects of rosiglitazone on bile duct ligation (BDL)-induced liver fibrosis and the involved mechanisms remain unknown. ⋯ Interestingly, rosiglitazone ameliorated BDL-induced liver injury in PPARγfl/fl mice but not in HepPPARγ KO mice. Mechanistically, rosiglitazone reduced BDL-induced collagen content by downregulating fibrotic related genes including transforming growth factor β1, α-smooth muscle actin and collagen type I α1, and decreased inflammation cytokine tumor necrosis factor α level by inhibiting phosphorylation of nuclear factor-κB in a PPARγ-dependent manner. Based on findings above, we demonstrated that rosiglitazone can ameliorate BDL-induced liver fibrosis in mice and confirmed its critical functions on fibrosis by regulating NF-κB-TNF-α pathway in a PPARγ-dependent manner.
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Biochem. Biophys. Res. Commun. · Sep 2019
Anti-inflammatory effect of artemisinin on uric acid-induced NLRP3 inflammasome activation through blocking interaction between NLRP3 and NEK7.
Artemisinin is a potent anti-malarial agent that plays a potent role in regulating inflammatory disorders. NEK7 is a major interacting partner with NLRP3 in NLRP3 inflammasome. The aim of this study was to clarify the anti-inflammatory effect of artemisinin on activation of uric acid-induced NLRP3 inflammasome through regulation of NEK7. ⋯ This study revealed that artemisinin inhibited activation of NLRP3 inflammasome by suppressing interaction between NEK7 and NLRP3 in uric acid-induced inflammation.