Urea stress is more akin to EGF exposure than to hypertonic stress in renal medullary cells

Tian, Wei; Cohen, David

doi:10.1152/ajprenal.00031.2002

Cited by 22 publications

(36 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VIIIB), transporters and channels reported to be regulated in this manner include several of the aquaporins, NKCC1, ROMK channels, NHE1 and -2, and the Na ϩ -K ϩ -ATPase. Microarray screening has also been applied, showing that ϳ12,000 transcripts are downregulated, and 4,000 upregulated (990,991), and the expression of tonicity-sensitive proteins has been studied by proteomics approaches (1021). The expression of the two-pore K ϩ channel TASK-2, which is important in RVD in EAT cells (see Ref.…”

Section: Other Proteins Regulated At the Transcriptional Level Aftmentioning

confidence: 99%

Physiology of Cell Volume Regulation in Vertebrates

Hoffmann

Lambert²,

Pedersen³

2009

Physiological Reviews

1,284

1,677

View full text Add to dashboard Cite

The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most cases, activation of volume regulatory osmolyte transport. After acute swelling, cell volume is regulated by the process of regulatory volume decrease (RVD), which involves the activation of KCl cotransport and of channels mediating K+, Cl−, and taurine efflux. Conversely, after acute shrinkage, cell volume is regulated by the process of regulatory volume increase (RVI), which is mediated primarily by Na+/H+exchange, Na+-K+-2Cl−cotransport, and Na+channels. Here, we review in detail the current knowledge regarding the molecular identity of these transport pathways and their regulation by, e.g., membrane deformation, ionic strength, Ca2+, protein kinases and phosphatases, cytoskeletal elements, GTP binding proteins, lipid mediators, and reactive oxygen species, upon changes in cell volume. We also discuss the nature of the upstream elements in volume sensing in vertebrate organisms. Importantly, cell volume impacts on a wide array of physiological processes, including transepithelial transport; cell migration, proliferation, and death; and changes in cell volume function as specific signals regulating these processes. A discussion of this issue concludes the review.

show abstract

Section: Other Proteins Regulated At the Transcriptional Level Aftmentioning

confidence: 99%

Physiology of Cell Volume Regulation in Vertebrates

Hoffmann

Lambert²,

Pedersen³

2009

Physiological Reviews

1,284

1,677

View full text Add to dashboard Cite

show abstract

“…In an unbiased screen, we identified COX-2 as one of the genes most prominently upregulated by hypertonicity in the renal medullary mIMCD3 cell model (41). Because other tonicity-inducible phenomena are potentially dependent on transactivation of the EGF recep-tor (EGFR) kinase (e.g., Refs.…”

mentioning

confidence: 99%

Hypertonic induction of COX-2 expression in renal medullary epithelial cells requires transactivation of the EGFR

Zhao

Tian

Tai

et al. 2003

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

.-Hypertonic stress increases expression of cyclooxygenase-2 (COX-2) in renal medullary epithelial and interstitial cells. Because hypertonic COX-2 expression is, in part, sensitive to inhibition of the ERK MAPK, an effector of activated receptor tyrosine kinases such as the EGF receptor, we investigated a role for this receptor in signaling to COX-2 expression. Hypertonic stress increased COX-2 expression at the mRNA and protein levels at 6 and 24 h of hypertonic treatment. Two potent, specific inhibitors of the EGF receptor kinase, AG-1478 and PD-153035, abrogated this effect. These inhibitors also blocked the ability of hypertonic stress to increase PGE 2 release; in addition, they partially blocked tonicity-dependent phosphorylation of ERK but not of the related MAPKs, JNK or p38. Pharmacological inhibition of ERK activation partially blocked tonicity-dependent COX-2 expression. Hypertonic induction of COX-2 was likely transcriptionally mediated, as NaCl stress increased luciferase reporter gene activity under control of the human COX-2 promoter, and this effect was also sensitive to inhibition of the EGF receptor kinase. Metalloproteinase action is required for transactivation of the EGF receptor. Pharmacological inhibition of metalloproteinase function blocked tonicity-inducible COX-2 expression. Furthermore, the effect of hypertonicity on COX-2 expression was also evident in the EGF-responsive Madin-Darby canine kidney and 3T3 cell lines but was virtually absent from the EGF-unresponsive (and EGF receptor null) Chinese hamster-derived CHO cell line. Taken together, these data indicate that hypertonicitydependent COX-2 expression in medullary epithelial cells requires transactivation of the EGF receptor and, potentially, ectodomain cleavage of an EGF receptor ligand.hypertonicity; heparin-binding epidermal growth factor; kidney; cylooxygenase HYPERTONICITY IS A fundamental, phylogenetically ubiquitous environmental stressor. In mammals, few tissues are exposed to wide ranges of ambient tonicity; one exception is the renal medulla where osmolality may exceed 1 osmol/kgH 2 O. A number of genes have been described whose expression is upregulated by hypertonic stress in renal medullary cells both in vitro and in vivo. Most are regulated by activation or synthesis of the tonicity-responsive transcription factor, TonEBP/NFAT5, and its subsequent interaction with its cognate cis-acting element, the tonicity enhancer element/osmotic response element (TonE/ORE; reviewed in Ref. 18).Cyclooxygenases (COX) are oxidoreductases that catalyze the conversion of membrane arachidonic acid to PGH 2 , a precursor of all prostaglandins, thromboxanes, and prostacyclins (39). There are at least two [and perhaps more (6)] isoforms of COX; COX-1 is constitutively and nearly ubiquitously expressed, whereas the inducible COX-2 isoform is primarily expressed in kidney and brain. COX-2, as a key mediator of inflammation, may be upregulated by a variety of cell activators, including mitogens, hormones, and environmental stressors (3, 2...

show abstract

“…16). At moderate concentrations that do not induce cell death, urea activates transcription of a set of genes including many transcription factors in a manner analogous to epidermal growth factor (17). Urea has also been shown to alleviate the hypertonic stress: addition of urea protects from hypertonicity-induced cell death in both acute phases (14) and chronic phases (6) despite further elevation of osmolality.…”

Section: Discussionmentioning

confidence: 99%

Distinct cellular pathways for resistance to urea stress and hypertonic stress

Lee

Choi

Kwon

2011

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Lee SD, Choi SY, Kwon HM. Distinct cellular pathways for resistance to urea stress and hypertonic stress. Am J Physiol Cell Physiol 300: C692-C696, 2011. First published December 22, 2010; doi:10.1152/ajpcell.00150.2010.-During antidiuresis with elevated vasopressin, urea accumulates in the renal medulla to very high concentrations, imposing considerable cellular stress. How local cells cope with urea stress is relevant to the whole kidney because the renal medulla is the major site of residence for the renal stem cells. Previous studies showed that renal cells were incapable of preconditioning in moderate urea concentrations to enhance resistance to urea stress. Instead, preconditioning in moderately high salinity (moderate hypertonicity) has been shown to promote resistance to urea stress due to the induction of the molecular chaperone heat shock protein 70 (Hsp70), which is mediated by the transcription factor tonicityresponsive enhancer binding protein (TonEBP). Here we report that cell lines derived from the kidney and fibroblasts display enhanced resistance to urea stress after pretreatment in moderate, nonstressful concentrations of urea. Using TonEBP knockdown and immunoblot analyses, we demonstrate that TonEBP and Hsp70 are dispensable for the increased resistance to urea stress. These data suggest that cells in the renal medulla are capable of overcoming urea stress by activating distinct cellular pathways. tonicity-responsive enhancer binding protein; heat shock protein 70; hypertonicity; renal medulla OSMOLALITY IN THE RENAL MEDULLA is high due to the operation of urinary concentrating mechanism. The cortex is isotonic but the osmolality gradually increases along the cortico-medullary axis starting from the outer medulla down to the tip of the papilla, where tissue osmolality reaches over 2,500 mosmol/ kgH 2 O in rodents during antidiuresis with elevated vasopressin (see Ref. 1 for a review). Urea and salt, two principal solutes in the renal medulla, differ in their osmotic action. Salt distributes mainly in the interstitium, i.e., excluded from the cell, and imposes hypertonic stress to the cell. While urea is an effective osmotic agent driving water reabsorption in the collecting duct, it is generally not excluded from the cell due to high membrane permeability.Despite the differences in their osmotic action, both hyperosmotic salt (hypertonicity) and urea impose cellular stress as they kill renal cells in culture in a dose-dependent manner (8,14). Underlying cellular mechanisms involved in the stress appear distinct for the two solutes since urea-induced cell death is not associated with reduced RNA and protein synthesis like hypertonicity-induced cell death (14). On the other hand, cells in the renal medulla in situ cope with the hyperosmolality without signs of distress as cell death is not detectable even during severe antidiuresis (15,19). Kidney-derived cells in culture can be preconditioned to enhance resistance to hyperAddressfor reprint requests and other correspondence: H. Moo Kwon, 655 ...

show abstract

Urea stress is more akin to EGF exposure than to hypertonic stress in renal medullary cells

Abstract: Tian, Wei, and David M. Cohen. Urea stress is more akin to EGF exposure than to hypertonic stress in renal medullary cells.

Cited by 22 publications

References 41 publications

Physiology of Cell Volume Regulation in Vertebrates

Physiology of Cell Volume Regulation in Vertebrates

Hypertonic induction of COX-2 expression in renal medullary epithelial cells requires transactivation of the EGFR

Distinct cellular pathways for resistance to urea stress and hypertonic stress

Contact Info

Product

Resources

About