[Effect of resveratrol on PTEN expression and fibrosis of renal tubular epithelial cells in a high-glucose environment].

This study explored the effects of resveratrol(Res) on the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) and the fibrosis of rat renal tubular epithelial cells in a high-glucose environment and the possible mechanism underlying the fibrosis reduction. After the pretreatment of rat renal tubular epithelial cells(NRK-52 E) cultured in a high-glucose condition with Res or PTEN inhibitor SF1670, they were divided into several groups, i.e., normal glucose(NG), normal glucose + SF1670(NS), high glucose(HG), high glucose + SF1670(HS), high glucose + Res at different concentrations(5, 10, 25 µmol·L~(-1)). The expression and distribution of E-cadherin and α-SMA in renal tubular epithelial cells were observed by immunofluorescence cytochemistry. The protein expression levels of PTEN, E-cadherin, α-SMA, p-Akt~((Thr308)) and collagen Ⅳ were determined by Western blot. Real-time PCR was employed to detect the expression of PTEN mRNA. Compared with the NG group, the HG group witnessed the reduced expression of PTEN mRNA, PTEN protein and E-cadherin protein, but saw the increased expression of α-SMA, p-Akt~((Thr308)) and collagen Ⅳ proteins. Besides, with the increase in Res concentration, the expression levels of PTEN mRNA, PTEN protein and E-cadherin protein gradually increased, while those of α-SMA, collagen Ⅳ, p-Akt~((Thr308)) proteins gradually decreased in the Res groups, showing a dose-effect dependence, compared with the HG group. No distinct difference was found between the NS group and the NG group. The expression level of E-cadherin was even lower and those of α-SMA, p-Akt~((Thr308)), and collagen Ⅳ were higher in the HS group than in the HG group, with no marked difference shown in the two groups in terms of PTEN mRNA and protein. Although the PTEN inhibitor did not affect PTEN, the expression changes of the other proteins were opposite to the results after Res treatment and the fibrosis was aggravated, which suggested that SF1670 promoted the fibrosis by inhibiting PTEN, activating Akt and increasing the synthesis of collagen Ⅳ and other extracellular matrix. The results show that Res can antagonize the high glucose-mediated fibrosis of renal tubular epithelial cells. This may be achieved via the up-regulation of PTEN and the inhibition of PI3 K/Akt signaling pathway.

Ferulic acid protects PC12 neurons against hypoxia by inhibiting the p-MAPKs and COX-2 pathways.

OBJECTIVES: Hypoxia induces cellular oxidative stress that is associated with neurodegenerative diseases. Here, the protective effects of ferulic acid (FA) on hypoxia-induced neurotoxicity in PC12 cells were evaluated. MATERIALS AND METHODS: We investigated the effect of FA on PC12 cells subjected to hypoxia stress, in vitro. RESULTS: FA increased cell viability, prevented membrane damage (LDH release), scavenged free radicals, increased superoxide dismutase (SOD) activity, and attenuated the elevation of intracellular free Ca(2+), lipid peroxidation, apoptosis (evaluated by TUNEL staining) and PGE2 production in hypoxia-stressed PC12 cells. MAPKs were activated during hypoxia. FA reduced p-p38 MAPK, caspase-3, and COX-2 activation which correlated well with diminished LDH release in PC12 cells under hypoxia. Furthermore, FA reduced lipid peroxidation in PC12 cells subjected to hypoxia. CONCLUSION: Taken together, these results indicate that FA antioxidant effects could partly be involved in inhibition of p38 MAPK pathway and apoptosis through scavenging ROS in hypoxia-stressed PC12 cells.

Expression of connexin 36 in central nervous system and its role in epileptic seizure.

OBJECTIVE: This review discusses the experimental and clinical studies those show the expression of connexin 36 in the central nervous system and the possible role of connexin 36 in epileptic seizure. DATA SOURCES: All articles used in this review were mainly searched from PubMed published in English from 1996 to 2012. STUDY SELECTION: Original articles and reviews were selected if they were related to the expression of connexin 36 in the central nervous system and its role in epilepsy. RESULTS: The distribution of connexin 36 is developmentally regulated, cell-specific and region-specific. Connexin 36 is involved in some neuronal functions and epileptic synchronization. Changes in the connexin 36 gene and protein were accompanied by seizures. Selective gap junction blockers have exerted anticonvulsant actions in a variety of experiments examined in both humans and experimental animals. CONCLUSIONS: Connexin 36 plays an important role in both physiological and pathological conditions in the central nervous system. A better understanding of the role of connexin 36 in seizure activity may contribute to the development of new therapeutic approaches to treating epilepsy.

Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation.

BACKGROUND: Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. METHODS: Rodents (male FVB mice and Sprague-Dawley rats) were fed with sesamin extract (90% of sesamin and 10% sesamolin), 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA), neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12 cells and microglial BV-2 cells. RESULTS: Treatment with sesamin extract (30 mg/kg) significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA) from 145% to 117% (p=0.017) and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p=0.013). The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. CONCLUSIONS: Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.