In vivo and in vitro osmotic regulation of HSP-70 and prostaglandin synthase gene expression in kidney cells

Cowley, Benjamin D.; Muessel, Michelle J.; Douglass, D.; Wilkins, Walter L.

doi:10.1152/ajprenal.1995.269.6.f854

Cited by 34 publications

(46 citation statements)

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“…In this context, Cox inhibitors have been shown to reduce the survival of IMCD cells kept under high osmolarities in culture, pointing to cellular protective effects of Cox-derived prostanoids (24). It has been demonstrated that an increase of papillary tonicity by dehydration increases not only Cox-2 (22-24) but also Cox-1 expression in the inner medulla of rats (23). Cell culture experiments with IMCD cells confirmed a stimulation of Cox-2 expression by high osmolarity mediated by ERK, JNK-2, and p38 kinases (24).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of Cox-2 in the inner medulla has already been shown to be influenced by the osmolarity (22)(23)(24), and we found in this study that furosemide reduced the osmolarity of the urine from 1550 Ϯ 108 mosmol/L in untreated to 480 Ϯ 33 mosmol/L in furosemide-treated rats; we, therefore, considered the possibility that it may be the low osmolarity that causes the downregulation of Cox-1 and to a lesser extent of Cox-2 expression in the inner medulla.…”

Section: Influence Of Furosemide Treatment On Pge 2 Concentrationmentioning

confidence: 99%

mentioning

confidence: 99%

“…Conversely, their expression is stimulated by high-salt diet (20,21), and as far as Cox-2 is concerned, by water deprivation (22,23). Conflicting data exist about the expression of Cox-1 in states of water deprivation, which were reported not to influence (22) or to increase Cox-1 expression in the renal medulla of rats (23). The expression of Cox-2 of cultured inner medullary collecting duct (IMCD) cells has been shown to be dependent on the osmolarity of the medium, in such way that high osmolarities lead to an increased expression of Cox-2 (20,24).…”

mentioning

confidence: 99%

“…On the other hand, loop diuretics are known to lower the tonicity in the renal medulla (29). It has been proposed that the expression of Cox-2 in the renal medulla changes in parallel with the tonicity (22)(23)(24); it is, therefore, also conceivable that loop diuretics could downregulate the expression of cyclooxygenases in the renal medulla.…”

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confidence: 99%

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Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla

Castrop¹,

Vitzthum²,

Schumacher³

et al. 2002

Journal of the American Society of Nephrology

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Abstract. It is well known that loop diuretics enhance the renal excretion of prostanoids; therefore, this study aimed to characterize the influence of loop diuretics on the intrarenal expression of cyclooxygenases, which are the key enzymes for prostanoid formation. Male Sprague-Dawley rats were infused with furosemide (12 mg/kg per d) for 6 d, and the expression of cyclooxygenase-1 and -2 (Cox-1 and Cox-2) was analyzed in the different kidney zones. Furosemide increased Cox-2 mRNA expression approximately twofold in the cortex, but it left Cox-1 mRNA expression unaltered there. In the outer medulla, furosemide changed neither Cox-1 nor Cox-2 mRNA expression. In the inner medulla, however, furosemide decreased Cox-1 and Cox-2 mRNA levels to approximately 30% and 60% of their control levels, respectively. The downregulation of mRNA was paralleled by a decrease of Cox protein in the collecting ducts and interstitial cells. Moreover, tissue prostaglandin E 2 (PGE 2 ) concentrations in the papilla were markedly decreased by furosemide to about 30% of the control level. Furosemide lowered urine osmolality from 1550 mosmol/kg to 480 mosmol/ kg; therefore, further consideration was given to the influence of tonicity as a possible mediator of the effects of furosemide on the Cox expression. Water loading was therefore used to reduce the medullary tonicity by a second maneuver. Water loading led to a similar reduction in papillary Cox mRNA expression and PGE 2 content like furosemide. To investigate the influence of the osmolarity on the expression of Cox and the production of PGE 2 under defined in vitro conditions, inner medullary collecting duct cells were incubated with culture medium containing graded amounts of NaCl ranging from 200 mmol/L to 600 mmol/L, and Cox-1 and Cox-2 mRNA abundance were determined after 24 h an 48 h. Cox-1 and Cox-2 mRNA abundance changed in parallel with the osmolarity. The data suggest that loop diuretics decrease the expression of cyclooxygenases and consequently tissue PGE 2 concentrations in the kidney inner medulla. This effect could be related to the breakdown of the papillary osmotic gradient induced by loop diuretics.

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Section: Discussionmentioning

confidence: 99%

Section: Influence Of Furosemide Treatment On Pge 2 Concentrationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla

Castrop¹,

Vitzthum²,

Schumacher³

et al. 2002

Journal of the American Society of Nephrology

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Osmotic regulation of the heat shock response in primary rat hepatocytes

1998

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The influence of cell hydration and taurine on the heat shock response was studied in primary rat hepatocytes. Heat-induced accumulation of inducible heat shock protein 70 (HSP70) mRNA and protein was increased under hypoosmotic conditions. In contrast, hyper-osmotic exposure blocked the HSP70 response during an 8-hour recovery, and this was paralleled by a reduction of overall protein synthesis and an impairment of thermotolerance. Taurine counteracted the hyper-osmotic inhibition of heat-induced HSP70 expression, but increased overall protein synthesis only slightly. A rapid and transient activation of the stress-activated protein kinase, JNK-2, was triggered by hyper-osmolarity, whereas the JNK-2 response to hypoosmolarity was delayed. JNK-2 activation in response to heat was suppressed by hypo-osmolarity, but was markedly increased under hyper-osmotic conditions. The Cell volume alterations induced by either aniso-osmotic environments or under the influence of hormones, oxidative stress, or cumulative substrate uptake represent an independent signal, which modulates cell function by changes in the cytoskeletal arrangement, metabolic activities, protein phosphorylation, and gene expression (for review, see Häuss-inger 1 ). Whereas cell shrinkage supports a catabolic situation in the liver, cell swelling exerts growth factor-like effects, e.g., by stimulation of protein and glycogen synthesis 2,3 and rapid stimulation of the mitogen-activated protein kinases, Erk-1 and Erk-2. 4,5 The hepatocellular hydration state was also found to modulate the tolerance of the liver against different forms of stress. For example, liver injury induced by reactive oxygen intermediates was amplified during hyper-osmotic perfusion of the rat liver, whereas hypo-osmolarity mediated protection against oxidative damage. 6,7 This was in part caused by osmotic modulation of stress-induced Kupffer cell activation. 7 However, there is evidence for a role of parenchymal cell hydration for hepatoprotection: hypo-osmotic liver perfusion was shown to increase canalicular bile excretion and the generation of reduced nicotinamide adenine dinucleotide via stimulating the pentose phosphate shunt, 6,8 whereas hyperosmolarity was suggested to create some oxidative stress by itself in rat liver parenchymal cells 8 and rat hepatoma cells. 9 The aggravation of ischemia/reoxygenation-induced liver injury by hyper-osmolarity was abolished in the presence of taurine, 7 which was recently identified as an osmolyte in liver parenchymal, Kupffer, and sinusoidal endothelial cells. [10][11][12] The heat shock protein, HSP70, can be induced by various stresses such as heat, arsenite, ethanol, infections, and heavy metals. 13 HSP70 was shown to mediate thermotolerance, but also protects against many other types of stress by stabilization of native protein structures. 13,14 Besides heat shock proteins, compatible organic osmolytes, which are accumulated inside the cells in response to long-term hyper-osmotic challenge, may prevent stress-induced protein denatu...

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Chronic Salinity Adaptation Modulates Hepatic Heat Shock Protein and Insulin-like Growth Factor I Expression in Black Sea Bream

et al. 2002

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In vivo and in vitro osmotic regulation of HSP-70 and prostaglandin synthase gene expression in kidney cells

Cited by 34 publications

References 0 publications

Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla

Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla

Osmotic regulation of the heat shock response in primary rat hepatocytes

Chronic Salinity Adaptation Modulates Hepatic Heat Shock Protein and Insulin-like Growth Factor I Expression in Black Sea Bream

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