Tissue-specific ceramide response in the chronically hypoxic rat model mimicking cyanotic heart disease.
OBJECTIVE
Acute hypoxia is associated with apoptosis and increase in ceramide levels in various organs. To assess the effect of chronic hypoxia on ceramide accumulation in the lungs and kidneys, we utilized an animal model mimicking cyanotic heart disease.


METHODS
Rats were placed in a hypoxic environment at birth and oxygen levels were maintained at 10% in an air-tight Plexiglas chamber. Controls remained in room air. Animals were sacrificed and the lung and kidneys were harvested and weighed at 1 and 4 weeks, respectively. Ceramide levels were measured using a modified diacylglycerol kinase assay.


RESULTS
Significant polycythemia developed in the hypoxic rats at 1 and 4 weeks. Indexed lung and kidney masses were significantly increased in the hypoxic animals as compared to controls at 1 and 4 weeks, respectively. The ceramide levels in the hypoxic lungs and kidneys were not significantly different from control groups at 1 and 4 weeks. [Ceramide/phosphate ratio in the kidneys was 1.28 +/- 0.17 (C) versus 1.18 +/- 0.12 (H) at 1 week; P = 0.39, and 1.46 +/- 0.08 (C) versus 1.33 +/- 0.15 (H) at 4 weeks (P = 0.44)] and [ceramide/phosphate ratio (pmol/nmol) in the lungs was 2.29 +/- 0.14 (C) versus 1.98 +/- 0.12 (H) at 1 week (P = 0.17), and 2.42 +/- 0.16 (C) versus 2.30 +/- 0.05 (H) at 4 weeks, P = 0.34].


CONCLUSIONS
The response of lungs and kidneys to chronic hypoxia includes increase in indexed mass and lack of ceramide accumulation. This is similar to the response previously reported in the chronically hypoxic brain and heart. Thus, various organs appear to have similar ceramide response pattern to chronic hypoxia.
Bitar
Fadi F
FF
Department of Pediatrics, American University of Beirut-Medical Center, Riad El Solh, P.O. Box 11-6023, A#22, Beirut 11072020, Lebanon. saad@aub.edu.lb
Mroueh
Salman
S
El Khatib
Mohamad
M
Bitar
Hala
H
Tarrabain
Mohammed
M
El Sabban
Marwan
M
Obeid
Mounir
M
Nasser
Michel
M
Dbaibo
Ghassan S
GS
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D002518:Ceramides / Q000378:metabolism*; D003490:Cyanosis; D004195:Disease Models, Animal; D006330:Heart Defects, Congenital / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D009929:Organ Size; D010710:Phosphates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014020:Tissue Extracts / Q000737:chemistry
D002518:Ceramides; D008055:Lipids; D010710:Phosphates; D014020:Tissue Extracts