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Carnosine Protects Mouse Podocytes from High Glucose Induced Apoptosis through PI3K/AKT and Nrf2 Pathways
Kunxiao Zhao1, Ying Li1, Ziqiang Wang2
1Department of Nephrology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province 050051, China.
Abstract:
Diabetic nephropathy is the complication of diabetes mellitus that can lead to chronic renal failure. Reactive oxygen species (ROS) production plays an important role in its pathological process. Previous studies showed that carnosine may reduce diabetic nephropathy by antioxidant effect. However, the molecular mechanism of its antioxidant was not fully understood. In the current study, we developed high glucose containing different concentrations of carnosine to reduce ROS levels and podocytes apoptosis, and Cell Counting Kit-8 test was used to observe the cell viability. Carnosine (5-20mM) was found to protect mouse podocytes (MPC5) cells from HG-induced injury. Quantitative real-time PCR, Western blotting, and immunofluorescence staining revealed that high glucose induced ROS levels and podocytes apoptosis were downregulated by PI3K/AKT and Nrf2 signaling pathways. The current findings suggest that carnosine may reduce ROS levels and MPC5 cells apoptosis by PI3K/AKT and Nrf2 signaling pathways activation.
Insights
Carnosine protects kidney cells from diabetes complications by reducing oxidative stress and apoptosis. It activates PI3K/AKT and Nrf2 pathways, offering a potential treatment for diabetic nephropathy.
Area of Science:
- Nephrology
- Diabetology
- Molecular Biology
Background:
- Diabetic nephropathy, a diabetes complication, can cause chronic renal failure.
- Reactive oxygen species (ROS) are key players in diabetic nephropathy's pathology.
- Carnosine exhibits antioxidant properties, but its precise mechanism in diabetic nephropathy is unclear.
Purpose of the Study:
- To investigate carnosine's protective effects on high glucose-induced injury in mouse podocytes (MPC5).
- To elucidate the molecular mechanisms underlying carnosine's antioxidant and anti-apoptotic actions.
Main Methods:
- MPC5 cells were exposed to high glucose (HG) with varying carnosine concentrations.
- Cell viability was assessed using the Cell Counting Kit-8 assay.
- ROS levels and apoptosis were measured using quantitative real-time PCR, Western blotting, and immunofluorescence staining.
Main Results:
- Carnosine (5-20mM) protected MPC5 cells against HG-induced injury.
- High glucose-induced ROS production and podocyte apoptosis were significantly downregulated by carnosine.
- These protective effects were mediated through the activation of the PI3K/AKT and Nrf2 signaling pathways.
Conclusions:
- Carnosine demonstrates protective effects against diabetic nephropathy-related kidney cell injury.
- Carnosine reduces ROS levels and podocyte apoptosis by activating PI3K/AKT and Nrf2 signaling pathways.
- Carnosine represents a potential therapeutic agent for managing diabetic nephropathy.
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