scholarly journals Impaired calcium homeostasis via advanced glycation end products promotes apoptosis through endoplasmic reticulum stress in human nucleus pulposus cells and exacerbates intervertebral disc degeneration in rats

FEBS Journal ◽  
2019 ◽  
Vol 286 (21) ◽  
pp. 4356-4373 ◽  
Author(s):  
Rongjin Luo ◽  
Yu Song ◽  
Zhiwei Liao ◽  
Huipeng Yin ◽  
Shengfeng Zhan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Intervertebral Disc ◽  
Advanced Glycation End Products ◽  
Calcium Homeostasis ◽  
Intervertebral Disc Degeneration ◽  
Advanced Glycation ◽  
Nucleus Pulposus Cells ◽  
Glycation End Products ◽  
End Products

scholarly journals The AGE receptor, OST48 drives podocyte foot process effacement and basement membrane expansion in experimental diabetic kidney disease via promotion of endoplasmic reticulum stress

2019 ◽  
Author(s):  
Aowen Zhuang ◽  
Felicia YT Yap ◽  
Domenica McCarthy ◽  
Sally A. Penfold ◽  
Karly C. Sourris ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Kidney Disease ◽  
Endoplasmic Reticulum Stress ◽  
Advanced Glycation End Products ◽  
Diabetic Kidney Disease ◽  
Advanced Glycation ◽  
Diabetic Kidney ◽  
Glycation End Products ◽  
End Products ◽  
Foot Process

AbstractThe accumulation of advanced glycation end products is implicated in the development and progression of diabetic kidney disease. No study has examined whether stimulating advanced glycation clearance via receptor manipulation is reno-protective in diabetes. Podocytes, which are early contributors to diabetic kidney disease and could be a target for reno-protection. To examine the effects of increased podocyte oligosaccharyltransferase-48 on kidney function, glomerular sclerosis, tubulointerstitial fibrosis and proteome (PXD011434), we generated a mouse with increased oligosaccharyltransferase-48kDa subunit abundance in podocytes driven by the podocin promoter. Despite increased urinary clearance of advanced glycation end products, we observed a decline in renal function, significant glomerular damage including glomerulosclerosis, collagen IV deposition, glomerular basement membrane thickening and foot process effacement and tubulointerstitial fibrosis. Analysis of isolated glomeruli identified enrichment in proteins associated with collagen deposition, endoplasmic reticulum stress and oxidative stress. Ultra-resolution microscopy of podocytes revealed denudation of foot processes where there was co-localization of oligosaccharyltransferase-48kDa subunit and advanced glycation end-products. These studies indicate that increased podocyte expression of oligosaccharyltransferase-48kDa subunit results in glomerular endoplasmic reticulum stress and a decline in kidney function.

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