Chemical anoxia of tubular cells induces activation of c-Src and its translocation to the zonula adherens

Cyanide (CN)-induced chemical anoxia of cultured mouse proximal tubular (MPT) cells increased the kinase activity of c-Src by approximately threefold. 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), a specific inhibitor of c-Src, prevented Src activation. CN also increased the...

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Published inAmerican journal of physiology. Renal physiology Vol. 53; no. 3; pp. F488 - F497
Main Authors SINHA, Diviya, ZHIYONG WANG, PRICE, Valerie R, SCHWARTZ, John H, LIEBERTHAL, Wilfred
Format Journal Article
LanguageEnglish
Published Bethesda, MD American Physiological Society 01.03.2003
Subjects
Biological and medical sciences
Cells
Chemicals
Fundamental and applied biological sciences. Psychology
Kidneys
Vertebrates: urinary system
Cell culture
Barrier function
Environmental factor
Src kinase
Activation
catenins
E-cadherin
Kidney
p120ctn
Proximal tube
tight junction
Permeability barrier
Translocation
Oxygen
Anoxia
Enzyme
Transferases
Rodentia
In vitro
ischemia
Vertebrata
Renal tubule
Mammalia
Depletion
Cell line
Urinary system
Mouse
Kinase
Animal
renal tubular cells
ATP
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Summary:Cyanide (CN)-induced chemical anoxia of cultured mouse proximal tubular (MPT) cells increased the kinase activity of c-Src by approximately threefold. 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), a specific inhibitor of c-Src, prevented Src activation. CN also increased the permeability of MPT cell monolayers, an event ameliorated by PP2. During CN treatment, the proteins of the zonula adherens (ZA; E-cadherin and the catenins) disappeared from their normal location at cell-cell borders and appeared within the cytosol. CN also resulted in the appearance of c-Src at cell-cell borders. PP2 prevented these CN-induced alterations in the distribution of ZA proteins and c-Src. CN also increased the association of c-Src with -catenin and p120 and induced a substantial increase in tyrosine phosphorylation of both catenins. PP2 prevented the CN-induced phosphorylation of these catenins. In summary, we show that CN-induced chemical anoxia activates c-Src and induces its translocation to cell-cell junctions where it binds to and phosphorylates -catenin and p120. Our findings suggest that these events contribute to the loss of the epithelial barrier function associated with chemical anoxia. [PERIODICAL ABSTRACT]
ISSN:1931-857X
1522-1466