Elevated phosphate mediates extensive cellular toxicity: from abnormal proliferation to cell death
He, P.; Mann-Collura, O.; Fling, J.; Edara, N.; Razzaque, M. S.
Show abstract
Inorganic phosphate (Pi) is an essential nutrient for human health. Due to our change in dietary pattern, dietary Pi overload engenders systematic phosphotoxicity, including excessive Pi related vascular calcification and chronic tissue injury. The molecular mechanisms of the seemingly distinct phenotypes remain elusive. In this study, we found that Pi directly mediates diverse cellular toxicity in a dose-dependent manner on a cell-based model. At moderately higher than physiological level, extracellular Pi promotes cell proliferation by activating AKT and extracellular signal-regulated kinase 1/2 (ERK1/2) cascades. By introducing additional Pi, we observed significant cell damage caused by the interwoven Pi related biological processes, including activation of mitogen-activated protein kinase (MAPK) signaling, endoplasmic reticulum (ER) stress, epithelial-mesenchymal transition (EMT) and apoptosis. Taken together, elevated extracellular Pi results in a broad spectrum of toxicity by rewiring complicated signaling networks that control cell growth, cell death, ER stress, and cell mobility.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Tumors cells with mismatch repair deficiency induce hyperactivation of Pyroptosis resistant to cell membrane damage but are more sensitive to Co-treatment of IFN-γ and TNF-α to PANoptosis 95%
- The oncogenic E3 ligase TRIP12 suppresses epithelial-mesenchymal transition (EMT) and metastasis-related processes through ZEB1/2 92%
- Effect of OASL on OXA-induced immunogenic cell death in gastric cancer via cGAS-STING pathway 92%
Similar papers in this journal
- Autophagy Decreases Alveolar Epithelial Cell Injury by Suppressing the NF-κB Signaling Pathway and Regulating the Release of Inflammatory Mediators 92%
- Copper impedes calcification of human aortic vascular smooth muscle cells through inhibition of osteogenic transdifferentiation and promotion of extracellular matrix stability 92%
- Real-time measurement of E2:ERα transcriptional activity in living cells. 92%
Similar papers in this journal
- The combination of lipopolysaccharide and D-galactosamine administration show positive genotoxic effect in mice liver 93%
- Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells 93%
- Cannabidiol (CBD) as a novel inhibitor of HLA-G expression in human choriocarcinoma cell line (JEG-3) 93%
Similar papers in this journal
- Pentoxifylline-induced Protein Expression Change in RAW 264.7 Cells as Determined by Immunoprecipitation-based High Performance Liquid Chromatography 95%
- Decorin inhibits glucose-induced lens epithelial cell apoptosis via suppressing p22phox-p38 MAPK signaling pathway 94%
- The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.