Does the colonic H,K-ATPase also act as an Na,K-ATPase?

Cougnon, Marc; Bouyer, Philippe; Planelles, Gabrielle; Jaisser, Frédéric

doi:10.1073/pnas.95.11.6516

Cited by 76 publications

(57 citation statements)

References 28 publications

(20 reference statements)

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“…As shown in Fig. 3, the presence of Na + /K + -ATPase a 1 subunit in the apical membranes can be excluded, allowing us to conclude that the previously measured Na + -and K + -stimulated ATPase activity found in the apical membranes of the colon is not due to Na + / K + -ATPase, but could be associated with some form(s) of the colonic H + /K + -ATPase, as suggested previously [27,28].…”

Section: Discussionsupporting

confidence: 52%

Action of palytoxin on apical H⁺/K⁺‐ATPase in rat colon

Scheiner‐Bobis¹,

Hübschle

Diener

2002

European Journal of Biochemistry

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Palytoxin stimulated a cation-dependent short-circuit current (Isc) in rat distal and proximal colon in a concentration-dependent fashion when applied to the mucosal surface of the tissue. The distal colon exhibited a higher sensitivity to the toxin. The palytoxin-induced Isc was blocked by vanadate but was resistant to ouabain or scilliroside, suggesting the conversion of a vanadate-sensitive H + /K + -ATPase into an electrogenic cation transporter. Cation substitution experiments with basolaterally depolarized tissues suggested an apparent permeability of the palytoxin-induced conductance of Na + >K + >Li + . Immunohistochemical control experiments confirmed the absence of the Na + /K + -ATPase in the apical membrane. Consequently, the pore-forming action of palytoxin is not restricted to Na + /K + -ATPase but is also observed with the colonic H + /K + -ATPase.Keywords: ATPase; colon; palytoxin; Isc; ion channel. P 2C -type ATPases are oligomeric enzymes consisting of a and b subunits [1]. The sodium pump from the plasma membranes of animal cells, a member of this group, generates a sodium gradient by pumping three Na + ions out of the cell and two K + ions into the cell for each ATP hydrolyzed [2]. This sodium gradient is the driving force of all secondarily active transporters and a presupposition for neuronal conduction of signals.The closest relatives of the sodium pump are the proton pumps from gastric and colon epithelial cells [3]. Although these pumps are not identical, they both catalyze an active secretion of protons driven by ATP hydrolysis. Unlike the sodium pump, however, both proton pumps are electroneutral: each transports one K + ion from the luminal side into the cytosol for each H + secreted.Several naturally occurring toxins have been identified as specific inhibitors of the sodium pump. Among them, the so-called cardioactive steroids or cardiac glycosides are not only known for their ability to selectively target the sodium pump but are widely used as effective medication for patients with heart failure or heart insufficiency [4]. Palytoxin, a toxin isolated from corals of the family Palythoa (e.g. Palythoa caribaeorum), is also a highly specific inhibitor of the sodium pump [5,6]. This most potent toxin (for rodents the LD 50 is 10-250 ng per kg of body weight) of animal origin can also be found together with ciguatoxin, maitotoxin, or gambierol in fishes that contribute to ciguatera poisonings [7,8]. Palytoxin is a rather unique and large molecule with the structural formula C 129 H 223 N 3 O 54 . The molecule can be divided into three subdomains, each connected by peptide bonds: a large N-terminal polyhydroxy x-amino acid followed by a dehydro-b-alanine residue and an aminopropanol group. The number of free hydroxyl groups is 42 [9,10]. Unlike the cardioactive steroids, however, which inhibit both ATP hydrolysis and ion conduction, palytoxin acts by arresting the ionophore of the pump into a permanently open state. Thus, in this case, inhibition of ATP hydrolysis is no longer associated ...

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Section: Discussionsupporting

confidence: 52%

Action of palytoxin on apical H⁺/K⁺‐ATPase in rat colon

Scheiner‐Bobis¹,

Hübschle

Diener

2002

European Journal of Biochemistry

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“…This finding is significant, because Na ϩ /K ϩ ATPase activity is reduced in rat distal colon before tumor development (31). Furthermore, this activity has localization and pharmacological properties that match those reported for this H ϩ /K ϩ ATPase with Na ϩ /K ϩ activity (28,29,31). Notably, the Na ϩ /K ϩ ATPase ␣ and ␤ subunits suppress cell motility through activation of PI3 kinase and interaction with annexin II (32); thus decreased abundance could signal increasing cell motility.…”

Section: Discussionmentioning

confidence: 49%

“…Interestingly, we observed reduced non-gastric H ϩ /K ϩ ATPase ␣ in tumors. Although annotated as an H ϩ /K ϩ ATPase, the rat form resembles a Na ϩ /K ϩ ATPase (75% sequence identity) and possesses significant Na ϩ /K ϩ activity (28,29). The mouse variant also is similar to mouse Na ϩ /K ϩ ATPase (NP 659149; 65% sequence identity; Blast score: 1373; E-value Ͻ 10 Ϫ100 ) (30), suggesting it may transport sodium.…”

Section: Discussionmentioning

confidence: 99%

Discovery and validation of colonic tumor-associated proteins via metabolic labeling and stable isotopic dilution

Huttlin

Chen²,

Barrett-Wilt³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The unique biology of a neoplasm is reflected by its distinct molecular profile compared with normal tissue. To understand tumor development better, we have undertaken a quantitative proteomic search for abnormally expressed proteins in colonic tumors from Apc Min/؉ (Min) mice. By raising pairs of Min and wild-type mice on diets derived from natural-abundance or 15 Nlabeled algae, we used metabolic labeling to compare protein levels in colonic tumor versus normal tissue. Because metabolic labeling allows internal control throughout sample preparation and analysis, technical error is minimized as compared with in vitro labeling. Several proteins displayed altered expression, and a subset was validated via stable isotopic dilution using synthetic peptide standards. We also compared gene and protein expression among tumor and nontumor tissue, revealing limited correlation. This divergence was especially pronounced for species showing biological change, highlighting the complementary perspectives provided by transcriptomics and proteomics. Our work demonstrates the power of metabolic labeling combined with stable isotopic dilution as an integrated strategy for the identification and validation of differentially expressed proteins using rodent models of human disease.colon cancer ͉ min mouse ͉ proteomics ͉ differential mass spectrometry ͉ transcriptomics

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“…Recently, Cougnon et al reported that HKc␣ cRNA could express both H-K and Na-K transport functions in Xenopus oocytes (15). As a result, it is not unlikely that our prior identification of Na,K-ATPase activity in apical membranes represented an expression of one or both H,K-ATPases and not basolateral membrane contamination.…”

mentioning

confidence: 85%