Transcription coactivator p300 promotes inflammation by enhancing p65 subunit activation in type 2 diabetes nephropathy.

BACKGROUND: p300, a transcription co-activator, plays an important role in multicellular organisms and inflammation. However, the mechanism of p300 in type 2 diabetes nephropathy (T2DN) remains largely unknown. Our aim is to explore the mechanism of p300 in T2DN. METHODS: A T2DN mice model was induced by db/db transgenic mice or a high fat diet for 24 weeks. The levels of IL-6 and TNF-α were examined by real-time PCR (RT-PCR) in the renal cortex and by an enzyme linked immunosorbent assay (ELISA) in the serum of the T2DN mice. p300 siRNA was used to knockdown the expression of p300, and His-tagged-p300 plasmid was used to overexpress the p300 protein level in podocytes. Hematoxylin-eosin staining (H&E) and Masson trichrome analysis were used to detect the kidney pathology in T2DN. RESULTS: The levels of IL-6 and TNF-α were significantly increased in T2DN. p300 was significantly increased in T2DN. Consistently, p300 silencing significantly suppressed the inflammatory response and the overexpression of p300 significantly promoted the production of IL-6 and TNF-α in T2DN. CONCLUSIONS: This study demonstrated that the production of IL-6 and TNF-α, and the expression of p300, were increased in T2DN. Furthermore, P300 significantly promoted the activation of the NF-κB subunit p65 through a direct association with p65 in T2DN, subsequently enhancing the production of IL-6 and TNF-α.

Neuroprotective effect of arctigenin via upregulation of P-CREB in mouse primary neurons and human SH-SY5Y neuroblastoma cells.

Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aß) production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1) protein level in neurons. In addition, neural apoptosis in both types of cells, inhibition of neurite outgrowth in human SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN) expression in neurons were also observed after H89 exposure. All these effects induced by H89 were markedly reversed by Arc treatment. Arc also significantly attenuated downregulation of the phosphorylation of CREB (p-CREB) induced by H89, which may contribute to the neuroprotective effects of Arc. These results demonstrated that Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced cell injury via upregulation of p-CREB.

Effects of salvianolic acid B on survival, self-renewal and neuronal differentiation of bone marrow derived neural stem cells.

Our previous study has demonstrated the therapeutic potential of bone marrow derived-neural stem cells (BM-NSCs) in CNS disorders; however, the beneficial effects are modest due to the poor survival and low neural differentiation frequency. Here, we demonstrate that salvianolic acid B (Sal B), a potent aqueous of a well known Chinese medicine herb, Salvia miltiorrhiza, possesses the ability to promote BM-NSCs proliferation in a dose dependent manner as verified by growth curve and Bromodeoxyuridine (BrdU) incorporation assays; While in differentiation medium, Sal B promoted nestin(+) BM-NSCs differentiated into greater numbers of NF-M(+) neurons and NG2(+) oligodendrocyte precursors, but fewer GFAP(+) astrocytes as verified by triple immunostaining and quantitative analysis; upon exposure to H(2)O(2), Sal B facilitated the cells survival, reduced LDH leakage, and inhibited apoptosis, displaying a dose-dependent neuroprotective effect on BM-NSCs. Sal B induced brain-derived neurotrophic factor (BDNF) production by BM-NSCs, which may be beneficial for the cells survival and differentiation in unfavourable environment. The collective evidence indicates that Sal B may be a potential drug to upgrade the therapeutic efficiency of BM-NSCs in CNS diseases.