Effects of Advanced Glycation End Products on RAGE-mediated Signaling Pathway in Retinal Pigment Epithelial Cell.

• Main Authors: Yi-Sheng Wu, 巫弈聖
• Other Authors: Chuen-Lin Huang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/05747751740250350002

碩士 === 國防醫學院 === 生理學研究所 === 101 === Advanced glycation end products (AGEs) are formed by aldehyde group of reducing sugars binding to the free amino group of protein. Previous studies have demonstrated that AGEs can be detected in the capillary walls in retina, which promote the capillary closure, increase permeability and further damage the capillaries. The present study tries to evaluate the effects of AGEs on diabetic retinopathy. Our preliminary data implied that AGEs could significantly promote human retinal pigment epithelial (RPE) cell migration but not alter the proliferation. Interestingly, in normoxia condition, AGEs can enhance the hypoxia inducible factor (HIF)-1protein expression in a dose and time dependent manners in RPE cells. The phosphorylation of Akt and p70S6K are involved AGEs-induced HIF1expression and the pretreatment with the PI3K inhibitor (LY294002) and the p70S6K inhibitor (Rapamycin) can significantly reverse the phenomenon. AGEs also induced RAGE expression in a dose dependent manner in RPE cells. However, AGEs do not alter the HIF-1mRNA expression and the PHD1, PHD2, PHD3 and VHL protein expressions. We also examined different kinds of AGEs including N-(carboxymethyl)lysine (CML) as well as methylglyoxal (MGO) and found that both AGEs can markedly induced HIF-1protein expression in RPE cells. Our study revealed the AGEs can enhance the HIF-1 protein expression through the RAGE and the PI3K/Akt/p70S6K pathways and it may provide an important pathogenic molecular mechanism for AGEs in diabetic retinopathy.