AGEs Inducing EPCs Apoptosis via ROS and p38 MAPK/JNK Pathways in Diabetic Vascular Complications

Area of Science:

• Cell Biology
• Vascular Biology
• Diabetology

Background:

• Endothelial progenitor cells (EPCs) are crucial for blood-vessel repair.
• Diabetes accelerates vascular damage, partly due to increased EPC apoptosis.
• Advanced glycation end products (AGEs) are implicated in diabetic complications, but their direct effect on EPCs is unclear.

Purpose of the Study:

• To investigate whether AGEs induce EPC apoptosis through oxidative stress and MAPK activation.
• To elucidate the underlying molecular mechanisms of AGEs-induced EPC apoptosis.

Main Methods:

• EPCs were isolated from rat bone marrow and treated with varying AGEs concentrations and durations.
• Apoptosis was assessed using Annexin V/PI staining and flow cytometry.
• Protein levels of Bax and Bcl-2, reactive oxygen species (ROS) generation, and MAPK pathway activation (JNK, p38MAPK) were analyzed.
• The effects of N-acetylcysteine (NAC), SP600125, and SB203580 were evaluated.

Main Results:

• AGEs significantly increased EPC apoptosis in a dose- and time-dependent manner.
• AGEs treatment elevated Bax expression, decreased Bcl-2 expression, and increased ROS generation.
• Antioxidant NAC and MAPK inhibitors (SP600125, SB203580) attenuated AGEs-induced apoptosis, ROS production, and modulated Bax/Bcl-2 levels.

Conclusions:

• AGEs trigger EPC apoptosis via oxidative stress and activation of the JNK and p38MAPK pathways.
• Targeting oxidative stress and MAPK signaling may offer therapeutic strategies for diabetic vascular complications by protecting EPCs.