ABSTRACT
OBJECTIVE To investigate the neuroprotective effects of quercetin on central neurons against chronic high glucose in central neurons, in relation to Nrf2/ARE/Glo-1 activation. METHODS SH- SY5Y cells were cultured with high glucose (HG, 70 mmol · L- 1), 4- fold of the normal glucose (17.5 mmol · L- 1). Quercetin was set three concentrations (5, 10, 20 μmol · L- 1), with Nrf2 activator sulforaphane (SFN) as a positive group (2.5 μmol·L-1). After 72 h, cells were collected for glyoxalase 1 (Glo-1) activity and GSH level were by spectrophotometry; advanced glycation end-products (AGEs) as well as nuclear Nrf2 and p-Nrf2 levels by immunofluorescence; Glo-1, γ-glutamycysteine synthase (γ-GCS), Nrf2 and p-Nrf2 protein levels by Western blotting, and Glo-1 and γ-GCS mRNA levels by real-time qPCR. RESULTS Quercetin increased the cell viability of SH-SY5Y cells, and upregulated the levels of Glo-1 activity, protein, and mRNA in SH-SY5Y cells cultured with HG, accompanied by the elevated levels of glutathione, a cofactor of Glo-1 activity, and the reduced levels of AGEs. Meanwhile, quercetin could increase p- Nrf2 and Nrf2 levels in nucleus as well as p- Nrf2 levels in cytosol of SH-SY5Y cells exposed to chronic HG, accompanied by the elevated protein expression and mRNA levels of γ- GCS, a known target gene of Nrf2/ARE signaling. Moreover, a PKC activator or a p38 MAPK inhibitor pretreatment could significantly increase the protein expression of γ-GCS in HG condition, but an alkylating agent for sulfydryl of cysteine in Keap 1, a negative regulator of Nrf2, pretreatment only showed an increased tendency of γ-GCS protein, compared with without pretreatment; however, after pretreatment with those tool drugs, co-treatment with quercetin and HG had similar results to those of single tool drug pretreatment followed by HG exposure. CONCLUSION Firstly, quercetin can enhance Glo-1 function in central neurons, which is mediated by activation of Nrf2/ARE pathway, then exerts the neuroprotection against HG induced damage; moreover, PKC and p38 MAPK pathways may be involved in Nrf2 inactivation in chronic HG condition.
ABSTRACT
Objective. To evaluate the relationship between waist-to-height ratio (WHtR) and glucose and lipid metabolism in Han adolescents aged 13-15 years. Methods. A study was conducted on 1665 Han adolescents aged 13-15 years. Measurements included height, weight, waist circumference, fasting plasma glucose(FPG), triglyceride and high-density lipoprotein cholesterol. The subjects were divided into two groups according to WHtR. Results.Compared with the control group (n=1340,WHtR<0.46), the abdominal obesity group(n=325,WHtRe”0.46) had significantly higher levels of body mass index (BMI) (26.3±3.6 vs 18.9±2.3), WHtR (0.51±0.04 vs 0.40±0.03), FPG (4.99±0.48 vs 4.86±0.46), and triglyceride (1.21±0.62 vs 0.87±0.41), and a lower level of high-density lipoprotein cholesterol (1.26±0.27 vs 1.46±0.30) (P<0.01). Logistic regression analysis showed that after controlling for age, sex and BMI, the elevated FPG and dyslipidemia risk odds ratios of the abdominal obesity group were 1.954 (95% CI :1.250~3.054) and 2.012 (95% CI:1.204~3.362) (P<0.01) respectively. When clustered, the odds ratio of elevated FPG and dyslipidemia was 6.659 (95% CI: 1.337~33.159) (P<0.01). Conclusions. The waist-to-height ratio is an appropriate measure to assess dyslipidemic-diabetic adolescents and should be used to guide early intervention with the aim of future prevention of these linked diseases.