Hypoxia increases transepithelial electrical conductance and reduces occludin at the plasma membrane in alveolar epithelial cells via PKC-ζ and PP2A pathway

Juan Carlos Caraballo; Cecilia Yshii; Maria L. Butti; Whitney Westphal; Jennifer A. Borcherding; Chantal Allamargot; Alejandro P. Comellas

doi:10.1152/ajplung.00109.2010

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Hypoxia increases transepithelial electrical conductance and reduces occludin at the plasma membrane in alveolar epithelial cells via PKC-ζ and PP2A pathway

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Hypoxia increases transepithelial electrical conductance and reduces occludin at the plasma membrane in alveolar epithelial cells via PKC-ζ and PP2A pathway

Juan Carlos Caraballo, Cecilia Yshii, Maria L. Butti, Whitney Westphal, Jennifer A. Borcherding, Chantal Allamargot and Alejandro P. Comellas

American journal of physiology. Lung cellular and molecular physiology, Vol.300(4), pp.L569-L578

04/01/2011

DOI: 10.1152/ajplung.00109.2010

PMCID: PMC3075095

PMID: 21257729

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Abstract

During pulmonary edema, the alveolar space is exposed to a hypoxic environment. The integrity of the alveolar epithelial barrier is required for the reabsorption of alveolar fluid. Tight junctions (TJ) maintain the integrity of this barrier. We set out to determine whether hypoxia creates a dysfunctional alveolar epithelial barrier, evidenced by an increase in transepithelial electrical conductance (G(t)), due to a decrease in the abundance of TJ proteins at the plasma membrane. Alveolar epithelial cells (AEC) exposed to mild hypoxia (PO2 = 50 mmHg) for 30 and 60 min decreased occludin abundance at the plasma membrane and significantly increased G(t). Other cell adhesion molecules such as E-cadherin and claudins were not affected by hypoxia. AEC exposed to hypoxia increased superoxide, but not hydrogen peroxide (H2O2). Overexpression of superoxide dismutase 1 (SOD1) but not SOD2 prevented the hypoxia-induced G(t) increase and occludin reduction in AEC. Also, overexpression of catalase had a similar effect as SOD1, despite not detecting any increase in H2O2 during hypoxia. Blocking PKC-zeta and protein phosphatase 2A (PP2A) prevented the hypoxia-induced occludin reduction at the plasma membrane and increase in G(t). In summary, we show that superoxide, PKC-zeta, and PP2A are involved in the hypoxia-induced increase in G(t) and occludin reduction at the plasma membrane in AEC.

Physiology

Respiratory System

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: Hypoxia increases transepithelial electrical conductance and reduces occludin at the plasma membrane in alveolar epithelial cells via PKC-ζ and PP2A pathway
Creators: Juan Carlos Caraballo - University of Iowa
Cecilia Yshii - University of Iowa
Maria L. Butti - University of Iowa
Whitney Westphal - University of Iowa
Jennifer A. Borcherding - University of Iowa
Chantal Allamargot - University of Iowa
Alejandro P. Comellas - University of Iowa
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.300(4), pp.L569-L578
DOI: 10.1152/ajplung.00109.2010
PMID: 21257729
PMCID: PMC3075095
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Publisher: Amer Physiological Soc
Number of pages: 10
Grant note: K01HL080966 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
Language: English
Date published: 04/01/2011
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; ICTS; Core Research Facilities; Internal Medicine
Record Identifier: 9984359932202771

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