Lung mitochondrial dysfunction in pulmonary hypertension syndrome. I. Site-specific defects in the electron transport chain.
The main objectives of this study were to determine a) site-specific defects in the electron transport chain of lung mitochondria of broilers with pulmonary hypertension syndrome (PHS), b) if these defects are attenuated by high dietary vitamin E, and c) if these defects have a genetic basis. In Experiment 1, lung mitochondria were isolated from broilers with and without PHS fed diets containing 15 IU and 100 IU dl-alpha-tocopherol acetate/kg (VE); the four treatments were control, VE, PHS, and VE-PHS, respectively. Hydrogen peroxide (H2O2) generation in isolated lung mitochondria was monitored by dichlorofluorosein (DCF) fluorescence in response to chemicals that inhibit electron flow at specific sites on the electron transport chain using a 96-well microplate with Cytoflour (excitation/emission 480/530 nm). Basal H2O2 production was higher in PHS than in control mitochondria. Differences in H2O2 production between control and PHS were magnified by inhibition of Complexes I and III (Coenzyme Q) of the respiratory chain in mitochondria. Functional defects in PHS mitochondria were attenuated by high dietary VE. In Experiment 2, basal H2O2 production and that following inhibition of Complexes I and III were lower in lung mitochondria isolated from broilers selected for genetic resistance to PHS than in nonselected birds in the base population. The results of this study indicate that site-specific defects in Complexes I and III may underlie lung mitochondrial dysfunction in broilers with PHS, that these defects are attenuated by high dietary vitamin E, and that these defects may be related to genetic predisposition to PHS.
Iqbal
M
M
Department of Poultry Science, Center of Excellence for Poultry Science, University of Arkansas, Fayetteville 72701, USA.
Cawthon
D
D
Wideman
R F
RF
Bottje
W G
WG
D000818:Animals; D001201:Ascites / Q000235:genetics / Q000378:metabolism / Q000662:veterinary; D002645:Chickens; D004579:Electron Transport / Q000187:drug effects* / Q000235:genetics; D006861:Hydrogen Peroxide / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D011201:Poultry Diseases / Q000235:genetics / Q000378:metabolism*; D014451:Ubiquinone / Q000037:antagonists & inhibitors; D014810:Vitamin E / Q000494:pharmacology*
D014451:Ubiquinone; D014810:Vitamin E; D006861:Hydrogen Peroxide