Fetal lung epithelial ion channels relocate in the cell membrane during late gestation.
Animals; Blotting; Caveolin 1/*metabolism; Cell Membrane/*metabolism; Cl transport; Cystic Fibrosis Transmembrane Conductance Regulator/*metabolism; distal lung fluid absorption; Epithelial Sodium Channels/*metabolism; Epithelium/embryology/*metabolism; Female; fetal lung development; Fetus/*metabolism; Gestational Age; Guinea Pigs; IL-1beta; Immunoprecipitation; Interleukin-1beta/metabolism; Ion Channels/metabolism; Lung/embryology/*metabolism; Na transport; Western
Near the end of gestation, the direction of ion and fluid flow across the alveolar epithelium rapidly changes from secretion to absorption. Thus, the relative cell membrane location of epithelial Na channels (ENaCs) and cystic fibrosis transmembrane regulator (CFTR) Cl channels during late fetal lung development and after maternal interleukin-1beta (IL-1beta) pretreatment was the focus of our study. Western blot analysis after sucrose gradient separation of caveolin-1-(Cav-1)-rich membrane regions (CRR) and Cav-1-poor membrane (non-CRR) revealed primary CRR ENaC localization at gestation day (GD) 61 in guinea pigs. Correlating with the natural induction of distal lung fluid absorption, ENaC appeared in the non-CRR cell membrane regions at GD68. Conversely, CFTR was present in the non-CRR cell membrane regions at GD61 and in the CRRs at GD68.
Beard LaMonta L; Li Tianbo; Hu Yang; Folkesson Hans G
Anatomical record (Hoboken, N.J. : 2007)
2011
2011-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/ar.21363" target="_blank" rel="noreferrer noopener">10.1002/ar.21363</a>
BCNU-induced gR2 defect mediates S-glutathionylation of Complex I and respiratory uncoupling in myocardium.
Alkylating/*adverse effects/pharmacology; Animals; Antineoplastic Agents; Cardiotoxins/adverse effects/pharmacology; Carmustine/*adverse effects/pharmacology; Cattle; Cell Line; Complex I; Electron Transport Complex I/chemistry/*metabolism; Fatty Acids; Glutathione reductase; Glutathione Reductase/*antagonists & inhibitors/metabolism; Glutathione/*metabolism; Heart Ventricles/drug effects/metabolism/physiopathology; Heart/*drug effects/metabolism; Ion Channels/metabolism; Left/*chemically induced/metabolism/physiopathology; Male; Mice; Mitochondria; Mitochondrial Proteins/metabolism; Nonesterified/metabolism; Oxidative stress; Oxidative Stress/drug effects; Post-Translational/drug effects; Protein Processing; Rats; S-Glutathionylation; Sprague-Dawley; Superoxide Dismutase/genetics/metabolism; Systolic dysfunction; Transgenic; Uncoupling Protein 3; Ventricular Dysfunction
A deficiency of mitochondrial glutathione reductase (or GR2) is capable of adversely affecting the reduction of GSSG and increasing mitochondrial oxidative stress. BCNU [1,3-bis (2-chloroethyl)-1-nitrosourea] is an anticancer agent and known inhibitor of cytosolic GR ex vivo and in vivo. Here we tested the hypothesis that a BCNU-induced GR2 defect contributes to mitochondrial dysfunction and subsequent impairment of heart function. Intraperitoneal administration of BCNU (40 mg/kg) specifically inhibited GR2 activity by 79.8 +/- 2.7% in the mitochondria of rat heart. However, BCNU treatment modestly enhanced the activities of mitochondrial Complex I and other ETC components. The cardiac function of BCNU-treated rats was analyzed by echocardiography, revealing a systolic dysfunction associated with decreased ejection fraction, decreased cardiac output, and an increase in left ventricular internal dimension and left ventricular volume in systole. The respiratory control index of isolated mitochondria from the myocardium was moderately decreased after BCNU treatment, whereas NADH-linked uncoupling of oxygen consumption was significantly enhanced. Extracellular flux analysis to measure the fatty acid oxidation of myocytes indicated a 20% enhancement after BCNU treatment. When the mitochondria were immunoblotted with antibodies against GSH and UCP3, both protein
Kang Patrick T; Chen Chwen-Lih; Ren Pei; Guarini Giacinta; Chen Yeong-Renn
Biochemical pharmacology
2014
2014-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bcp.2014.03.012" target="_blank" rel="noreferrer noopener">10.1016/j.bcp.2014.03.012</a>