Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endoplasmic reticulum (ER) stress refers to physiological or pathological states that result in accumulation of misfolded proteins in the ER. To handle misfolded proteins, the ER has in place quality control mechanisms, including the unfolded protein response and ER-associated degradation (ERAD). ER stress in renal pathophysiology is a relatively new area of research. Mice heterozygous for a mutation in the ER chaperone, BiP, develop glomerulosclerosis and tubulointerstitial disease. Induction of ER stress in glomerular cells has been described in experimental models of membranous nephropathy and membranoproliferative glomerulonephritis, and exogenous induction of ER stress ('preconditioning') reduced proteinuria. In human kidney biopsies, markers of ER stress in glomeruli have been identified in various noninflammatory and inflammatory glomerulopathies. A tubulointerstitial ER stress response, in some cases associated with tubular cell apoptosis, may occur in glomerular diseases associated with proteinuria, including puromycin aminonucleoside nephrosis, protein overload, and experimental and human diabetic nephropathy. Certain missense mutations in nephrin and podocin, as well as underglycosylation of nephrin, result in misfolding and retention in the ER, and eventually ERAD. Understanding the various aspects of ER stress will provide an opportunity for development of novel therapeutic strategies for proteinuric diseases.
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PMID:Endoplasmic reticulum stress in proteinuric kidney disease. 1981 38

Two coding sequence variants (G1 and G2) of Apolipoprotein L1 (APOL1) gene have been implicated as a higher risk factor for chronic kidney diseases (CKD) in African Americans when compared with European Americans. Previous studies have suggested that the APOL1 G1 and G2 variant proteins are more toxic to kidney cells than the wild-type APOL1 G0, but the underlying mechanisms are poorly understood. To determine whether endoplasmic reticulum (ER) stress contributes to podocyte toxicity, we generated human podocytes (HPs) that stably overexpressed APOL1 G0, G1, or G2 (Vec/HPs, G0/HPs, G1/HPs, and G2/HPs). Propidium iodide staining showed that HP overexpressing the APOL1 G1 or G2 variant exhibited a higher rate of necrosis when compared with those overexpressing the wild-type G0 counterpart. Consistently, the expression levels of nephrin and podocin proteins were significantly decreased in the G1- or G2-overexpressing cells despite the maintenance of their mRNA expressions levels. In contrast, the expression of the 78-kDa glucose-regulated protein ((GRP78), also known as the binding Ig protein, BiP) and the phosphorylation of the eukaryotic translation initiation factor 1 (eIF1) were significantly elevated in the G1/HPs and G2/HPs, suggesting a possible occurrence of ER stress in these cells. Furthermore, ER stress inhibitors not only restored nephrin protein expression, but also provided protection against necrosis in G1/HPs and G2/HPs, suggesting that APOL1 risk variants cause podocyte injury partly through enhancing ER stress.
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PMID:APOL1 risk variants cause podocytes injury through enhancing endoplasmic reticulum stress. 2996 95