Differential expression of SLC30A10 and RAGE in mouse pups by early life lead exposure.

BACKGROUND: SLC30A10 and RAGE are widely recognized as pivotal regulators of Aß plaque transport and accumulation. Prior investigations have established a link between early lead exposure and cerebral harm in offspring, attributable to Aß buildup and amyloid plaque deposition. However, the impact of lead on the protein expression of SLC30A10 and RAGE has yet to be elucidated. This study seeks to confirm the influence of maternal lead exposure during pregnancy, specifically through lead-containing drinking water, on the protein expression of SLC30A10 and RAGE in mice offspring. Furthermore, this research aims to provide further evidence of lead-induced neurotoxicity. METHODS: Four cohorts of mice were subjected to lead exposure at concentrations of 0 mM, 0.25 mM, 0.5 mM, and 1 mM over a period of 42 uninterrupted days, spanning from pregnancy to the weaning phase. On postnatal day 21, the offspring mice underwent assessments. The levels of lead in the blood, hippocampus, and cerebral cortex were scrutinized, while the mice's cognitive abilities pertaining to learning and memory were probed through the utilization of the Morris water maze. Furthermore, Western blotting and immunofluorescence techniques were employed to analyze the expression levels of SLC30A10 and RAGE in the hippocampus and cerebral cortex. RESULTS: The findings revealed a significant elevation in lead concentration within the brains and bloodstreams of mice, mirroring the increased lead exposure experienced by their mothers during the designated period (P < 0.05). Notably, in the Morris water maze assessment, the lead-exposed group exhibited noticeably diminished spatial memory compared to the control group (P < 0.05). Both immunofluorescence and Western blot analyses effectively demonstrated the concomitant impact of varying lead exposure levels on the hippocampal and cerebral cortex regions of the offspring. The expression levels of SLC30A10 displayed a negative correlation with lead doses (P < 0.05). Surprisingly, under identical circumstances, the expression of RAGE in the hippocampus and cortex of the offspring exhibited a positive correlation with lead doses (P < 0.05). CONCLUSION: SLC30A10 potentially exerts distinct influence on exacerbated Aß accumulation and transportation in contrast to RAGE. Disparities in brain expression of RAGE and SLC30A10 may contribute to the neurotoxic effects induced by lead.

Effects of folic acid on oxidative damage of kidney in lead-exposed rats.

Introduction: Lead (Pb) has many applications in daily life, but in recent years, various problems caused by lead exposure have aroused people's concern. Folic acid is widely found in fruits and has received more attention for its antioxidant function. However, the role of folic acid in lead-induced kidney injury in rats is unclear. This study was designed to investigate the effects of folic acid on oxidative stress and endoplasmic reticulum stress in the kidney of rats caused by lead exposure. Methods: Forty specific pathogen-free male Rattus norvegicus rats were randomly divided into control, lead, intervention, and folic acid groups. The levels of SOD, GSH-Px, GSH, and MDA were measured by biochemical kits. The protein levels of Nrf2, HO-1, CHOP, and GRP78 were measured by immunofluorescence. Results: This study showed that lead exposure increased the blood levels of lead in mice. However, the intervention of folic acid decreased the levels of lead, but the difference was not statistically significant. Lead exposure causes oxidative stress by decreasing kidney SOD, GSH-Px, and GSH levels and increasing MDA levels. However, folic acid alleviated the oxidative damage caused by lead exposure by increasing the levels of GSH-Px and GSH and decreasing the levels of MDA. Immunofluorescence results showed that folic acid intervention downregulated the upregulation of kidney Nrf2, HO-1, GRP78, and CHOP expression caused by lead exposure. Discussion: Overall, folic acid alleviates kidney oxidative stress induced by lead exposure by regulating Nrf2 and HO-1, while regulating CHOP and GRP78 to mitigate apoptosis caused by excessive endoplasmic reticulum stress.

Mechanism of mitigating effect of wheat germ peptides on lead-induced oxidative damage in PC12 cells.

It is well known that lead-induced neurotoxicity is closely related to oxidative stress. According to previous reports, wheat germ peptides (WGPs) isolated from wheat germ have been shown to have potent antioxidant capacity. This study hypothesized that WGPs could protect PC12 cells from lead-induced oxidative stress. Here, the protecting-efficacies of WGPs were investigated in PC12 cells that were pretreated with WGPs (200 µM, 4 h) and exposed to lead (10 µM, 24 h). The antioxidant capacity was assessed by cell viability, ROS, MDA, SOD, CAT, GR, GPx, GSH, and GSSG. The experimental results showed that WGP3, WGP8, and WGP9 could reverse the reduction of cell viability caused by lead exposure. Lead exposure causes oxidative stress by increasing the levels of ROS and MDA. Moreover, the decrease in the levels of SOD, CAT, GPx, GR, and GSH/GSSG could be observed. However, WGP3, WGP8, and WGP9 can protect PC12 cells against lead-induced oxidative stress by reversing these phenomena. The protein expression of TXNIP, Keap1, and Nrf2 was characterized by western blotting, and the results illustrated that lead exposure up-regulated the expression of TXNIP and Keap1 and down-regulated the expression of Nrf2, and WGP3, WGP8, and WGP9 could improve the antioxidant capacity of PC12 cells by reversing this phenomenon. Therefore, the present study demonstrated that WGP3, WGP8, and WGP9 may protect against lead-induced oxidative stress in PC12 cells by regulating the TXNIP/Keap1/Nrf2 pathway.

Antioxidant activity and protective effect of wheat germ peptides in an in vitro celiac disease model via Keap1/Nrf2 signaling pathway.

Celiac disease (CD) is an allergic intestinal disease caused primarily by gliadin and is widespread in the population. Alpha gliadin peptide causes cellular damage by substantially increasing cellular reactive oxygen species (ROS) levels. In this study, we examined the protective effect of 25 wheat germ peptides (WGPs) on the ɑ-gliadin peptide (P31-43)-treated Caco-2 cells. The experimental results showed that three peptides, WGP2, WGP7, and WGP11, significantly promoted cell viability and greatly alleviated the damage of Caco-2 cells by P31-43. According the assay of ROS, The three WGPS significantly reduced ROS to normal levels, which were elevated by P31-43 peptide. The results in terms of antioxidant-related enzymes showed that WGPs significantly increased catalase (CAT), Glutathione Reductases (GR), Glutathione peroxidase (GPx), and Glutathione (GSH)/ oxidized Glutathione (GSSG) levels, thus significantly enhancing the antioxidant level of cells. By studying the key protein expression levels of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2) pathway, the results show that WGPs could activate Nrf2 and glutamate-cysteine ligase catalytic subunit (GCLC) up-regulation. For glutamate-cysteine ligase modifier (GCLM), WGP2 and WGP7 lead to its down-regulation, while WGP11 leads to its significant up-regulation.The present study found that peptides from wheat germ can effectively mitigate the cellular damage induced by the ɑ-gliadin peptide, which provides a new perspective for the prevention and treatment of CD.

Alleviating Effects of Black Soybean Peptide on Oxidative Stress Injury Induced by Lead in PC12 Cells via Keap1/Nrf2/TXNIP Signaling Pathway.

Many researchers have found that Pb exposure can cause oxidative stress damage to the body's tissue. Black soybean peptide (BSP) has a variety of physiological functions, especially in terms of oxidative stress. Nevertheless, the mitigation function of BSPs on Pb-induced oxidative stress damage in PC12 cells has not been clearly defined. In this study, cell viability was detected by CCK8. Oxidative stress indicators, such as ROS, GSH/GSSG, MDA, SOD, CAT, GPx, and GR, were tested with biochemical kit. Protein expression of Keap1, Nrf2, and TXNIP was measured by Western blot. Compared with the control group, Pb reduced the cell viability of PC12 cells. However, BSP treatment significantly increased the viability of PC12 cells induced by lead exposure (p < 0.05). Lead can enrich the contents of MDA and ROS, but decrease the amount of CAT, SOD, GR, GPx, and GSH/GSSG in PC12 cells, while BSP can alleviate it (p < 0.05). Lead can enhance the expression of Keap1 and TXNIP proteins, but reduce Nrf2 expression. In contrast, BSPs reversed this phenomenon (p < 0.05). BSPs can alleviate oxidative stress injury induced by lead in PC12 cells through the Keap1/Nrf2/TXNIP signaling pathway.

Alleviating effects of pea peptide on oxidative stress injury induced by lead in PC12 cells via Keap1/Nrf2/TXNIP signaling pathway.

Background: Lead poisoning causes an oxidative stress response - a key "bridge" connecting various pathways - in the human body. Oxidative stress usually implies an imbalance between pro-oxidants and antioxidants. Moreover, Nrf2, Keap1, and TXNIP proteins play an essential role in oxidative stress. Some studies showed that pea peptides could alleviate the oxidative stress response. However, the effect and mechanism of pea peptide on oxidative stress response induced by lead in PC12 cells has not been reported. Aim: Investigating the effect and mechanism of pea peptides in alleviating oxidative damage in PC12 cells induced by lead. Methods: In this study, cell viability was measured by CCK8 (Cell Counting Kit-8). Superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), reactive oxygen species (ROS), and lipid peroxidation (MDA) were measured using the corresponding Biochemical kits. The Keap1, Nrf2, and TXNIP protein expressions were tested using Western blot. Results: Pea peptides PP3, PP4, and PP6 could reverse the decrease of cell viability caused by lead exposure (P < 0.05), the elevation of ROS and MDA caused by lead exposure, and the decrease of CAT, SOD, GR, GPx, and GSH/GSSG caused by lead exposure (P < 0.05). Moreover, PP3, PP4, and PP6 could reduce the elevated expression of Keap1 and TXNIP caused by lead exposure; and increase the expression of Nrf2 (P < 0.05). Conclusion: PP3, PP4, and PP6 can alleviate lead-induced oxidative stress damage in PC12 cells, and the Nrf2/Keap1/TXNIP signaling pathway may play an essential role in this process.