Far-infrared protects vascular endothelial cells from advanced glycation end products-induced injury via PLZF-mediated autophagy in diabetic mice

Cheng-Hsien Chen,Tso-Hsiao Chen,Meng-Jun Wei,Li-Yu Hong,Jia-Rung Chen,San-Liang Lee,Yung-Ho Hsu,Tz-Chong Chou,Ching-Min Hsu,Yuh-Feng Lin,Mei-Yi Wu,Cai-Mei Zheng,I-Jen Chiu

doi:10.1038/srep40442

Abstract

The accumulation of advanced glycation end products (AGEs) in diabetic patients induces vascular endothelial injury. Promyelocytic leukemia zinc finger protein (PLZF) is a transcription factor that can be activated by low-temperature far-infrared (FIR) irradiation to exert beneficial effects on the vascular endothelium. In the present study, we investigated the influence of FIR-induced PLZF activation on AGE-induced endothelial injury both in vitro and in vivo. FIR irradiation inhibited AGE-induced apoptosis in human umbilical vein endothelial cells (HUVECs). PLZF activation increased the expression of phosphatidylinositol-3 kinases (PI3K), which are important kinases in the autophagic signaling pathway. FIR-induced PLZF activation led to autophagy in HUVEC, which was mediated through the upregulation of PI3K. Immunofluorescence staining showed that AGEs were engulfed by HUVECs and localized to lysosomes. FIR-induced autophagy promoted AGEs degradation in HUVECs. In nicotinamide/streptozotocin-induced diabetic mice, FIR therapy reduced serum AGEs and AGEs deposition at the vascular endothelium. FIR therapy also reduced diabetes-induced inflammatory markers in the vascular endothelium and improved vascular endothelial function. These protective effects of FIR therapy were not found in PLZF-knockout mice. Our data suggest that FIR-induced PLZF activation in vascular endothelial cells protects the vascular endothelium in diabetic mice from AGE-induced injury.

Highlights

Many studies have revealed that advanced glycation end products (AGEs) play a critical role in promoting diabetic vascular dysfunction and diabetes development[5]
Two inhibitors of phosphatidylinositol-3 kinases (PI3Ks), 3-methyladenine (3-MA) and wortmannin, inhibited the anti-apoptotic effect of FIR in AGE-bovine serum albumin (BSA)-treated human umbilical vein endothelial cells (HUVECs) (Fig. 2d). These results reveal that FIR-induced PLZF nuclear translocation upregulates PI3Ks to inhibit AGE-BSA-induced apoptosis in HUVECs
Western blots revealed that FIR irradiation increased beclin-1 and light chain 3 (LC3)-II expression in HUVECs, which was blocked by PLZF siRNA transfection (Fig. 3b)

Summary

Introduction

Many studies have revealed that advanced glycation end products (AGEs) play a critical role in promoting diabetic vascular dysfunction and diabetes development[5]. PLZF siRNA transfection blocked the inhibitory effect of FIR on AGE-BSA-induced apoptosis in HUVECs (Fig. 2c). Western blots revealed that FIR irradiation increased beclin-1 and LC3-II expression in HUVECs, which was blocked by PLZF siRNA transfection (Fig. 3b). Beclin-1 siRNA transfection blocked the inhibitory effect of FIR on AGE-BSA-induced apoptosis in HUVECs (Fig. 3e).

Results

Conclusion