scholarly journals Potential Protection Effect of ER Homeostasis of N6-(2-Hydroxyethyl)adenosine Isolated from Cordyceps cicadae in Nonsteroidal Anti-Inflammatory Drug-Stimulated Human Proximal Tubular Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1577
Author(s):  
Charng-Cherng Chyau ◽  
Huei-Lin Wu ◽  
Chiung-Chi Peng ◽  
Shiau-Huei Huang ◽  
Chin-Chu Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Er Stress ◽  
Cell Damage ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Protein Levels ◽  
Cordyceps Cicadae ◽  
Proximal Tubular ◽  
Anti Inflammatory ◽  
Er Homeostasis

Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N6-(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK–2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex® LH–20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK–2 cells. The HK–2 cells were pretreated with HEA (10–20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production (p < 0.001) and gene expression of ATF–6, PERK, IRE1α, CDCFHOP, IL1β, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF- and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway.

scholarly journals Organelle Stress and Crosstalk in Kidney Disease

Kidney360 ◽  
2020 ◽  
Vol 1 (10) ◽  
pp. 1155-1162
Author(s):  
Sho Hasegawa ◽  
Reiko Inagi
Keyword(s):  
Kidney Disease ◽  
Er Stress ◽  
Calcium Homeostasis ◽  
Stress Responses ◽  
Primary Cilia ◽  
Proximal Tubular Cells ◽  
Cellular Homeostasis ◽  
Tubular Cells ◽  
Progression Of Kidney Disease ◽  
Proximal Tubular

Organelles play important roles in maintaining cellular homeostasis. Organelle stress responses, especially in mitochondria, endoplasmic reticula (ER), and primary cilia, are deeply involved in kidney disease pathophysiology. Mitochondria are the center of energy production in most eukaryotic cells. Renal proximal tubular cells are highly energy demanding and abundant in mitochondria. Mitochondrial dysfunctions in association with energy metabolism alterations produce reactive oxygen species and promote inflammation in proximal tubular cells, resulting in progression of kidney disease. The ER play critical roles in controlling protein quality. Unfolded protein response (UPR) pathways are the adaptive response to ER stress for maintaining protein homeostasis. UPR pathway dysregulation under pathogenic ER stress often occurs in glomerular and tubulointerstitial cells and promotes progression of kidney disease. The primary cilia sense extracellular signals and maintain calcium homeostasis in cells. Dysfunction of the primary cilia in autosomal dominant polycystic kidney disease reduces the calcium concentration in proximal tubular cells, leading to increased cell proliferation and retention of cyst fluid. In recent years, the direct interaction at membrane contact sites has received increased attention in association with the development of imaging technologies. The part of the ER that is directly connected to mitochondria is termed the mitochondria-associated ER membrane (MAM), which regulates calcium homeostasis and phospholipid metabolism in cells. Disruption of MAM integrity collapses cellular homeostasis and leads to diseases such as diabetes and Alzheimer disease. This review summarizes recent research on organelle stress and crosstalk, and their involvement in kidney disease pathophysiology. In addition, potential treatment options that target organelle stress responses are discussed.

scholarly journals Advanced Oxidation Protein Products Induce Hypertrophy and Epithelial-To-Mesenchymal Transition in Human Proximal Tubular Cells through Induction of Endoplasmic Reticulum Stress

2015 ◽  
Vol 35 (2) ◽  
pp. 816-828 ◽  
Author(s):  
Xun Tang ◽  
Guang Rong ◽  
Yang Bu ◽  
Shaojie Zhang ◽  
Min Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Er Stress ◽  
Total Protein ◽  
Epithelial To Mesenchymal Transition ◽  
Proximal Tubular Cells ◽  
Advanced Oxidation Protein Products ◽  
Mesenchymal Transition ◽  
Tubular Cells ◽  
Cell Hypertrophy ◽  
Proximal Tubular

Background: In chronic kidney disease (CKD), the accumulation of advanced oxidation protein products (AOPPs) is prevalent. Hypertrophy and epithelial-to-mesenchymal transition (EMT) of tubular cells are associated with the pathogenesis of CKD. However, whether AOPPs induce tubular-cell hypertrophy and EMT is unclear. In this study, we investigated the effect of AOPPs on human proximal tubular cells (HK-2 cells) and the mechanisms underlying tubular-cell hypertrophy and EMT in vitro. Methods: The mRNA and protein expression of CCAAT/enhancer-binding protein-homologous protein (CHOP), glucose-regulated protein (GRP) 78, p27, α-smooth muscle actin (α-SMA) and E-cadherin were evaluated by quantitative real-time PCR and western blot, respectively. Cell cycle was detected by flow cytometry. Bicinchoninic acid method was performed to measure total protein content. Results: AOPP treatment upregulated total protein expression, caused an increase in the percentage of G1-phase cells, and induced the overexpression of p27 and α-SMA, lowered the expression of E-cadherin. Furthermore, AOPP treatment induced the overexpression of GRP78 and CHOP. Moreover, the aforementioned effects were reversed following the treatment of cells with an NADPH oxidase inhibitor, a reactive oxygen species (ROS) scavenger, or salubrinal, which is an inhibitor of ER stress, whereas these effects were produced after exposure to thapsigargin, an inducer of ER stress. Conclusion: Our results suggest that AOPPs induced HK-2-cell hypertrophy and EMT by inducing ER stress, which was likely mediated by ROS. These findings could facilitate the development of novel therapeutic strategies for suppressing the progression of CKD.

scholarly journals Abrogation of store-operated Ca2+ entry protects against crystal-induced ER stress in human proximal tubular cells

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Farai C. Gombedza ◽  
Samuel Shin ◽  
Yianni L. Kanaras ◽  
Bidhan C. Bandyopadhyay
Keyword(s):  
Er Stress ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular

Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter

2007 ◽  
Vol 292 (1) ◽  
pp. F395-F403 ◽  
Author(s):  
Hiroko Segawa ◽  
Setsuko Yamanaka ◽  
Akemi Onitsuka ◽  
Yuka Tomoe ◽  
Masashi Kuwahata ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Apical Membrane ◽  
Hypophosphatemic Rickets ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Transporter Protein ◽  
Protein Levels ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

Hereditary hypophosphatemic rickets with hypercalciuria results from mutations of the renal type IIc Na-Pi cotransporter gene, suggesting that the type IIc transporter plays a prominent role in renal phosphate handling. The goal of the present study was to investigate the regulation of the type IIc Na-Pi cotransporter by parathyroid hormone (PTH). Type IIc Na-Pi cotransporter levels were markedly increased in thyroparathyroidectomized (TPTX) rats. Four hours after administration of PTH, type IIc transporter protein levels were markedly decreased in the apical membrane fraction but recovered to baseline levels at 24 h. Immunohistochemical analyses demonstrated the presence of the type IIc transporter in the apical membrane and subapical compartments in the proximal tubular cells in TPTX animals. After administration of PTH, the intensity of immunoreactive signals in apical and subapical type IIc transporter decreased in the renal proximal tubular cells in TPTX rats. Colchicine completely blocked the internalization of the type IIc transporter. In addition, leupeptin prevented the PTH-mediated degradation of the type IIa transporter in lysosomes but had no effect on PTH-mediated degradation of the lysosomal type IIc transporter. In PTH-treated TPTX rats, the internalization of the type IIc transporter occurred after administration of PTH(1–34) (PKA and PKC activator) or PTH(3–34) (PKC activator). Thus the present study demonstrated that PTH is a major hormonal regulator of the type IIc Na-Pi cotransporter in renal proximal tubules.

scholarly journals Molecular mechanisms of glucose action on angiotensinogen gene expression in rat proximal tubular cells

1999 ◽  
Vol 55 (2) ◽  
pp. 454-464 ◽  
Author(s):  
Shao-LING Zhang ◽  
Janos G. Filep ◽  
Thomas C. Hohman ◽  
Shiow-SHIH Tang ◽  
Julie R. Ingelfinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Angiotensinogen Gene ◽  
Proximal Tubular
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