Apolipoprotein (apo)B mRNA editing is mediated by a multiprotein editosome complex. Apobec-1 is the catalytic component of this complex, but other proteins involved in editing have not been identified. We used the yeast two-hybrid system to identify an apobec-1-interacting protein, ABBP-1. ABBP-1 contains 331 amino acid residues and is identical to a previously reported human type A/B hnRNP except for a 47-residue insertion at its C-terminal region. It contains typical RNP motifs at its N-terminal half and glycine-rich motifs in the C-terminal region. Northern blot analysis indicates that ABBP-1 mRNA is distributed in multiple human tissues. By deletion analysis, we mapped the apobec-1-binding region to the glycine-rich domain. ABBP-1 also binds to apoB mRNA transcripts around the editing site and can be UV-cross-linked to them in vitro. Immnodepletion of ABBP-1 from an active apoB mRNA editing tissue extract inhibits its editing activity. Down-regulation of ABBP-1 in an apobec-1-expressing HepG2 cell line by transfection with an antisense ABBP-1 cDNA construct leads to inhibition of endogenous apoB mRNA editing. We conclude that ABBP-1 is an apobec-1-interacting protein that may play an important role in apoB mRNA editing.
Systemic changes in metabolite concentrations are most likely the result of cells switching to glycolysis to maintain energy homeostasis. The results suggest that metabonomics may also facilitate the discovery of novel cancer biomarkers and allows the stratification of tumors under different pathophysiological conditions, which might be a valuable future tool for RCC detection and possibly other cancers.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons; however, its crucial mechanism of the metabolic changes of neurotransmitters remains ambiguous. The pathological mechanism of PD might involve cerebral metabolism perturbations. In this study, ex vivo proton nuclear magnetic resonance ((1)H NMR) was used to determine the level changes of 13 metabolites in the bilateral striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats. The results showed that, in the right striatum of 6-OHDA-induced PD rats, increased levels of glutamate (Glu) and γ-aminobutyric acid (GABA) concomitantly with decreased level of glutamine (Gln) were observed compared to the control. Whereas, in the left striatum of 6-OHDA-induced PD rats, increased level of Glu with decreased level of GABA and unchanged Gln were observed. Other cerebral metabolites including lactate, alanine, creatine, succinate, taurine, and glycine were also found to have some perturbations. The observed metabolic changes for Glu, Gln, and GABA are mostly likely the result of a shift in the steady-state equilibrium of the Gln-Glu-GABA metabolic cycle between astrocytes and neurons. The altered Gln and GABA levels are most likely as a strategy to protect neurons from Glu excitotoxic injury after striatal dopamine depletion. Changes in energy metabolism and tricarboxylic acid cycle might be involved in the pathogenesis of PD.
Background and Purpose: Renal fibrosis acts as the common pathway leading to the development of end-stage renal disease. Previous studies have shown that resveratrol has anti-fibrotic activity, but its potential molecular mechanisms of action are not well understood. Experimental Approach: The anti-fibrotic effects of resveratrol were assayed in a rat model of unilateral ureteral obstruction (UUO) in vivo and in fibroblasts and tubular epithelial cells (TECs) stimulated by TGF-β1 in vitro. Gene and protein expression levels were analysed by PCR, Western blotting, and immunohistochemical staining. Key Results: Resveratrol inhibits the myofibroblastic phenotype and fibrosis formation in UUO kidneys by targeting fibroblast-myofibroblast differentiation (FMD) and epithelial-mesenchymal transition (EMT). The anti-fibrotic effects of resveratrol correlated with decreased proliferation of TECs in the interstitium and tubules, resulting in suppressed activity of the proliferation-related signalling pathways, including that of the MAPK, PI3K/Akt, Wnt/β-catenin, and JAK2/STAT3 pathways. Resveratrol treatment suppressed TGF-β1-induced FMD and the expression of the myofibroblastic phenotype in fibroblasts in vitro by antagonizing the activation of proliferation-related signalling. Similarly, TGF-β1-mediated overactivation of the proliferation-related signalling in TECs induced EMT, and the myofibroblastic phenotype was suppressed by resveratrol. The anti-fibrotic and anti-proliferative effects of resveratrol were associated with the inactivation of Smad2/3 signalling and resulted in a partial reversal of FMD and EMT and the inhibition of the myofibroblastic phenotype.
Conclusions and Implications:Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in vivo and in vitro via proliferation-related pathways, making it a potential therapeutic agent for preventing renal fibrosis.
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