Abstract
Prostasin is a membrane-bound/secretive serine protease interacting with aldosterone and the epithelial sodium channel in the kidney. We and others have previously proposed the concept of stress-induced pressure natriuresis (SIPN) where increased urinary sodium excretion (UNaV) is coupled with elevated blood pressure (BP) in response to behavioral stress in normotensive adolescents. This study thus aimed to test the relationship between prostasin and pressure natriuresis using the SIPN model. A cohort of 102 normotensive black adolescents (mean age: 17.0 ± 1.2 y; 56% females) were placed on a controlled sodium (4000 ± 200 mg/d) and potassium (2600 ± 200 mg/d) diet for three days before testing. The SIPN protocol consisted of a 1-h baseline period, a 1-h stress period (competitive video game), and a 1-h recovery period. During the stress period, BP elevation was coupled with an increase in UNaV. Urinary prostasin concentration had more than a 2-fold reduction from baseline (38.4 ± 32.7 ng/mL) to stress (17.2 ± 16.0 ng/mL), and further declined during recovery (12.1 ± 16.2 ng/mL) (p < 0.001). Urinary prostasin was inversely correlated with UNaV during stress (r = −0.43, p = 0.0001), even after being normalized by urinary creatinine. Our data suggest that urinary prostasin could be a novel biomarker and/or mechanism for renal pressure natriuresis in normotensive black adolescents.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BP:
-
blood pressure
- ENaC:
-
epithelial sodium channel
- SIPN:
-
stress-induced pressure natriuresis
- UNaV:
-
urinary sodium excretion
References
Guyton AC, Coleman TG 1969 Quantitative analysis of the pathophysiology of hypertension. Circ Res 24: 1–19
Garty H, Palmer LG 1997 Epithelial sodium channels: function, structure, and regulation. Physiol Rev 77: 359–396
Gormley K, Dong Y, Sagnella GA 2003 Regulation of the epithelial sodium channel by accessory proteins. Biochem J 371: 1–14
Pratt JH 2005 Central role for ENaC in development of hypertension. J Am Soc Nephrol 16: 3154–3159
Vallet V, Chraibi A, Gaeggeler HP, Horisberger JD, Rossier BC 1997 An epithelial serine protease activates the amiloride-sensitive sodium channel. Nature 389: 607–610
Vallet V, Horisberger JD, Rossier BC 1998 Epithelial sodium channel regulatory proteins identified by functional expression cloning. Kidney Int Suppl 67: S109–S114
Chraibi A, Vallet V, Firsov D, Hess SK, Horisberger JD 1998 Protease modulation of the activity of the epithelial sodium channel expressed in Xenopus oocytes. J Gen Physiol 111: 127–138
Vuagniaux G, Vallet V, Jaeger NF, Pfister C, Bens M, Farman N, Courtois-Coutry N, Vandewalle A, Rossier BC, Hummler E 2000 Activation of the amiloride-sensitive epithelial sodium channel by the serine protease mCAP1 expressed in a mouse cortical collecting duct cell line. J Am Soc Nephrol 11: 828–834
Adachi M, Kitamura K, Miyoshi T, Narikiyo T, Iwashita K, Shiraishi N, Nonoguchi H, Tomita K 2001 Activation of epithelial sodium channels by prostasin in Xenopus oocytes. J Am Soc Nephrol 12: 1114–1121
Chen LM, Skinner ML, Kauffman SW, Chao J, Chao L, Thaler CD, Chai KX 2001 Prostasin is a glycosylphosphatidylinositol-anchored active serine protease. J Biol Chem 276: 21434–21442
Vallet V, Pfister C, Loffing J, Rossier BC 2002 Cell-surface expression of the channel activating protease xCAP-1 is required for activation of ENaC in the Xenopus oocyte. J Am Soc Nephrol 13: 588–594
Vuagniaux G, Vallet V, Jaeger NF, Hummler E, Rossier BC 2002 Synergistic activation of ENaC by three membrane-bound channel-activating serine proteases (mCAP1, mCAP2, and mCAP3) and serum- and glucocorticoid-regulated kinase (Sgk1) in Xenopus oocytes. J Gen Physiol 120: 191–201
Hughey RP, Mueller GM, Bruns JB, Kinlough CL, Poland PA, Harkleroad KL, Carattino MD, Kleyman TR 2003 Maturation of the epithelial Na+ channel involves proteolytic processing of the alpha- and gamma-subunits. J Biol Chem 278: 37073–37082
Rossier BC 2004 The epithelial sodium channel: activation by membrane-bound serine proteases. Proc Am Thorac Soc 1: 4–9
Kleyman TR, Myerburg MM, Hughey RP 2006 Regulation of ENaCs by proteases: an increasingly complex story. Kidney Int 70: 1391–1392
Hughey RP, Carattino MD, Kleyman TR 2007 Role of proteolysis in the activation of epithelial sodium channels. Curr Opin Nephrol Hypertens 16: 444–450
Carattino MD, Sheng S, Bruns JB, Pilewski JM, Hughey RP, Kleyman TR 2006 The epithelial Na+ channel is inhibited by a peptide derived from proteolytic processing of its alpha subunit. J Biol Chem 281: 18901–18907
Bruns JB, Carattino MD, Sheng S, Maarouf AB, Weisz OA, Pilewski JM, Hughey RP, Kleyman TR 2007 Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit. J Biol Chem 282: 6153–6160
Narikiyo T, Kitamura K, Adachi M, Miyoshi T, Iwashita K, Shiraishi N, Nonoguchi H, Chen LM, Chai KX, Chao J, Tomita K 2002 Regulation of prostasin by aldosterone in the kidney. J Clin Invest 109: 401–408
Wang C, Chao J, Chao L 2003 Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats. Am J Physiol Regul Integr Comp Physiol 284: R1031–R1036
Iwashita K, Kitamura K, Narikiyo T, Adachi M, Shiraishi N, Miyoshi T, Nagano J, Tuyen DG, Nonoguchi H, Tomita K 2003 Inhibition of prostasin secretion by serine protease inhibitors in the kidney. J Am Soc Nephrol 14: 11–16
Harshfield GA, Treiber FA, Davis H, Kapuku GK 2002 Impaired stress-induced pressure natriuresis is related to left ventricle structure in blacks. Hypertension 39: 844–847
Harshfield GA, Wilson ME, Hanevold C, Kapuku GK, Mackey L, Gillis D, Treiber FA 2002 Impaired stress-induced pressure natriuresis increases cardiovascularload in African American youths. Am J Hypertens 15: 903–906
Barbeau P, Litaker MS, Harshfield GA 2003 Impaired pressure natriuresis in obese youths. Obes Res 11: 745–751
Wilson ME, Harshfield GA, Ortiz L, Hanevold C, Kapuka G, Mackey L, Gillis D, Edmonds L, Evans C 2004 Relationship of body composition to stress-induced pressure natriuresis in youth. Am J Hypertens 17: 1023–1028
Harshfield GA, Wilson ME, McLeod K, Hanevold C, Kapuku GK, Mackey L, Gillis D, Edmonds L 2003 Adiposity is related to gender differences in impaired stress-induced pressure natriuresis. Hypertension 42: 1082–1086
Hanevold CD, Pollock JS, Harshfield GA 2008 Racial differences in microalbumin excretion in healthly adolescents. Hypertension 51: 334–338
Weinberger MH 1993 Racial differences in renal sodium excretion: relationship to hypertension. Am J Kidney Dis 21: 41–45
Falkner B 1990 Differences in blacks and whites with essential hypertension: biochemistry and endocrine. State of the art lecture. Hypertension 15: 681–686
Zhu H, Yan W, Ge D, Treiber FA, Harshfield GA, Kapuku G, Snieder H, Dong Y 2008 Relationships of cardiovascular phenotypes with healthy weight, at risk of overweight, and overweight in US youths. Pediatrics 121: 115–122
Mok SC, Chao J, Skates S, Wong K, Yiu GK, Muto MG, Berkowitz RS, Cramer DW 2001 Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology. J Natl Cancer Inst 93: 1458–1464
Hall JE 2003 The kidney, hypertension, and obesity. Hypertension 41: 625–633
Yu JX, Chao L, Chao J 1994 Prostasin is a novel human serine proteinase from seminal fluid. Purification, tissue distribution, and localization in prostate gland. J Biol Chem 269: 18843–18848
Yu JX, Chao L, Chao J 1995 Molecular cloning, tissue-specific expression, and cellular localization of human prostasin mRNA. J Biol Chem 270: 13483–13489
Chen LM, Chai KX 2002 Prostasin serine protease inhibits breast cancer invasiveness and is transcriptionally regulated by promoter DNA methylation. Int J Cancer 97: 323–329
Funder JW 1993 Aldosterone action. Annu Rev Physiol 55: 115–130
Connell JM, Davies E 2005 The new biology of aldosterone. J Endocrinol 186: 1–20
Olivieri O, Castagna A, Guarini P, Chiecchi L, Sabaini G, Pizzolo F, Corrocher R, Righetti PG 2005 Urinary prostasin: a candidate marker of epithelial sodium channel activation in humans. Hypertension 46: 683–688
Wilson DK, Sica DA, Miller SB 1999 Effects of potassium on blood pressure in salt-sensitive and salt-resistant black adolescents. Hypertension 34: 181–186
Wilson DK, Bayer L, Sica DA 1996 Variability in salt sensitivity classifications in black male versus female adolescents. Hypertension 28: 250–255
Author information
Authors and Affiliations
Corresponding authors
Additional information
Supported by grant HL077230 from National Heart, Lung, and Blood Institute.
Rights and permissions
About this article
Cite this article
Zhu, H., Chao, J., Guo, D. et al. Urinary Prostasin: A Possible Biomarker for Renal Pressure Natriuresis in Black Adolescents. Pediatr Res 65, 443–446 (2009). https://doi.org/10.1203/PDR.0b013e3181994b85
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e3181994b85
This article is cited by
-
Urinary prostasin in normotensive individuals: correlation with the aldosterone to renin ratio and urinary sodium
Hypertension Research (2013)
-
Urinary prostasin excretion is associated with adiposity in nonhypertensive African-American adolescents
Pediatric Research (2013)
-
Obesity related methylation changes in DNA of peripheral blood leukocytes
BMC Medicine (2010)
-
Prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells
Histochemistry and Cell Biology (2009)


