Hypoxic preconditioning (HPC) exerts a protective effect against hypoxic/ischemic brain injury, and one mechanism explaining this effect may involve the upregulation of hypoxia-inducible factor-1 (HIF-1). Autophagy, an endogenous protective mechanism against hypoxic/ischemic injury, is correlated with the activation of the HIF-1α/Beclin1 signaling pathway. Based on previous studies, we hypothesize that the protective role of HPC may involve autophagy occurring via activation of the HIF-1α/Beclin1 signaling pathway. To test this hypothesis, we evaluated the effects of HPC on oxygen-glucose deprivation/reperfusion (OGD/R)-induced apoptosis and autophagy in SH-SY5Y cells. HPC significantly attenuated OGD/R-induced apoptosis, and this effect was suppressed by the autophagy inhibitor 3-methyladenine and mimicked by the autophagy agonist rapamycin. In control SH-SY5Y cells, HPC upregulated the expression of HIF-1α and downstream molecules such as BNIP3 and Beclin1. Additionally, HPC increased the LC3-II/LC3-I ratio and decreased p62 levels. The increase in the LC3-II/LC3-I ratio was inhibited by the HIF-1α inhibitor YC-1 or by Beclin1-short hairpin RNA (shRNA). In OGD/R-treated SH-SY5Y cells, HPC also upregulated the expression levels of HIF-1α, BNIP3, and Beclin1, as well as the LC3-II/LC3-I ratio. Furthermore, YC-1 or Beclin1-shRNA attenuated the HPC-mediated cell viability in OGD/R-treated cells. Taken together, our results demonstrate that HPC protects SH-SY5Y cells against OGD/R via HIF-1α/Beclin1-regulated autophagy.
The invasive and infiltrative nature of tumor cells leads to the poor prognosis of glioma. Currently, novel therapeutic means to eliminate the tumor cells without damaging the normal brain tissue are still strongly demanded. Significant attentions had been paid to stem cell-based therapy and neural stem cell (NSC) had been considered as one of the efficient delivery vehicles for targeting therapeutic genes. However, whether the NSCs could directly affect glioma cells remains to be seen. In this study, both rat and human glioma cells (C6 and U251) were co-cultured with normal rat embryonic NSCs directly or in-directly. We found the survival, proliferation, invasion and migration of glioma cells were significantly inhibited, while the differentiation was not affected in the in vitro co-culture system. In nude mice, although no significant difference was observed in the tumor growth, survival status and time of tumor-bearing mice were significantly promoted when U251 cells were subcutaneously injected with NSCs. In coincidence with the suppression of glioma cell growth in vitro, expression of mutant p53 and phosphorylation of AKT, ERK1/2 decreased while the level of caspase-3 increased significantly. Our results suggested that normal NSCs could possess direct anti-glioma properties via inhibiting the glioma cell viability, proliferation, invasion and migration. It could be a very promising candidate for glioma treatment.
Sodium chloride is a major source of salt in human nutrition. It is well-known that long-term high-salt diet (HSD) was associated with the development of hypertension and cardiovascular disease, especially when sodium intake exceeds 5 g/day. 1 There is an emerging evidence that the consumptions of dietary sodium are usually excess of requirements in the form of salt in many countries among adults and childrens, and then, leading to the excess weight gain. 2 Strikingly, both experimental data from animal and epidemiological data from clinical investigations in human being demonstrated that long-term HSD may cause cognitive dysfunction and brain tissue damage in adult individuals. 3,4 Data from rodents reported that HSD impaired cognitive function without changing blood pressure. 5,6 Furthermore, HSD disturbed the short-and long-term memory of mouse with corresponding increases in hippocampal oxidative stress and deregulation of synaptic protein/neurotrophin. 6 The importance of adequate maternal nutrition during the development for offspring's long-term physical health has
Glioma is one of the most common and aggressive tumors in the brain. Significant attention has been paid to the potential use of neural stem/progenitor cells (NSCs/NPCs) as delivery vehicles to cure gliomas. However, whether the NSCs/NPCs or the factors they produced could make a contribution still remains to be seen. In this study, we focused on the inhibitory effects of the factors produced by NSCs/NPCs on the biological behavior of the glioma stem‐like cell in vitro. The human glioma cell line U87 was selected and the U87 stem‐like cells were addressed. After being cultured in the NSC condition medium (NSC‐CM), the viability and proliferation of U87 stem‐like cells were significantly reduced. The invasion of U87 stem‐like cells and the migration of U87 cells were also significantly decreased. However, no significant change was observed in regard to the astrocytic differentiation of U87 stem‐like cells. These indicated that NSCs/NPCs produced some factors and had an inhibitory effect on the growth and invasion but not the terminal differentiation of U87 stem‐like cells. It is worth paying attention to NSCs/NPCs as a high‐potential candidate for glioma treatment.
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