Journal article
Modulation of total ceramide and constituent ceramide species in the acutely and chronically hypoxic mouse heart at different ages
Prostaglandins & other lipid mediators, Vol.86(1), pp.49-55
2008
DOI: 10.1016/j.prostaglandins.2008.02.003
PMID: 18400538
Abstract
Ceramide has been implicated in regulatory processes vital for cell survival under different stressors, most notably hypoxia. Little has been done to investigate the contributions of the different ceramide species to the regulation of cell survival. This study aims to highlight the patterns of variation in total ceramide and its species in the growing and hypoxic mouse heart.
Mus musculus mice were placed in a hypoxic environment at birth. Control animals remained in room air. The hearts were extracted at different time points: 1 day, 1 week, 4 weeks, and 8 weeks. The total ceramide content and the amounts of component species were assayed by a modified diacylglycerol kinase assay and high-performance liquid chromatography–tandem mass spectroscopy, respectively. Data was collected from both ventricles in hypoxic and control conditions. There was significant polycythemia in the hypoxic versus control animals with a nearly twofold increase in hematocrit levels. Hypoxic right ventricle (RV) mass significantly increased over that of controls at different age groups. When ceramide content was compared in the hypoxic versus control animals, there was a significant increase at day 1 and a significant decrease at week 4 in the left ventricle, whereas a significant decrease was found in the RV at 1 week, 4 weeks, and 8 weeks. There was also a differential involvement of the RV with regard to levels of
N-palmitoyl-
d-erythro-sphingosine (C16-Cer) and its synthetic precursor dihydro-
N-palmitoyl-
d-erythro-sphinganine (DHC-16-Cer). The decrease in C16-Cer observed in both hypoxic and control RV's over time was paralleled by a significant increase in DHC-16-Cer in hypoxic (142.1
±
15.0
pmol;
p
<
0.05) but not control (52.8
±
4.0
pmol) RV's suggesting a role for DHC-16-Cer in the RV adaptive response to hypoxia. Another species,
N-arachidoyl-
d-erythro-sphingosine (C20-Cer), was specifically and significantly decreased in the hypoxic RV. These studies support the presence of distinct roles for different ceramide species and their precursors. A better assessment of cyanotic congenital heart disease in light of the mechanism and timing of cardiomyocyte death, will lead to punctual interventions and even novel cardioprotective strategies.
Details
- Title: Subtitle
- Modulation of total ceramide and constituent ceramide species in the acutely and chronically hypoxic mouse heart at different ages
- Creators
- Lama Noureddine - Department of Pediatrics, American University of Beirut-Medical Center, Beirut, LebanonRaed Azzam - Department of Pediatrics, American University of Beirut-Medical Center, Beirut, LebanonGeorges Nemer - Department of Biochemistry, American University of Beirut, Beirut, LebanonJacek Bielawski - Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, United StatesMichel Nasser - Department of Physiology, American University of Beirut, Riad El Solh, P.O. Box 11-6023, A#22, 11072020 Beirut, LebanonFadi Bitar - Department of Pediatrics, American University of Beirut-Medical Center, Beirut, LebanonGhassan S Dbaibo - Department of Pediatrics, American University of Beirut-Medical Center, Beirut, Lebanon
- Resource Type
- Journal article
- Publication Details
- Prostaglandins & other lipid mediators, Vol.86(1), pp.49-55
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.prostaglandins.2008.02.003
- PMID
- 18400538
- ISSN
- 1098-8823
- eISSN
- 2212-196X
- Language
- English
- Date published
- 2008
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094310002771
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