title: Regulation of the sphingolipid signaling pathways in the growing and hypoxic rat heart.
abstract: Sphingolipids (SLs) have a biomodulatory role in physiological as well as pathological cardiovascular conditions. This study aims to assess the variation of SL mediators and metabolizing enzymes in the growing and hypoxic rat heart. Sprague-Dawley rats were placed in a hypoxic environment at birth. Control animals remained in room air. In control animals, activities of acidic-sphingomyelinase (A-SMase), sphingomyelin synthase (SMS), glucosylceramide synthase (GCS), and ceramidase decreased with age in both ventricles whereas activity of neutral-sphingomyelinase (N-SMase) increased with age. Hypoxic RV mass was 171 and 229% that of controls, at 4 and 8 weeks, respectively. This was accompanied by an increase in RV myocardial ceramide synthesis, consumption and breakdown, with a net effect of suppression of ceramide accumulation and increase in diacylglycerol (DAG) concentration. In addition, significant increase in activities of: A-SMase by 26 and 29%, SMS by 108 and 40%, and ceramidase by 66 and 35%, in the hypoxic RV rats as compared to controls, was noted at 4 and 8 weeks of age, respectively. Sphingolipids and their regulating enzymes appear to play a role in adaptive responses to chronic hypoxia in the neonatal rat heart.
authors.affiliation: Department of Pediatrics, American University of Beirut-Medical Center, Beirut, Lebanon.
authors.forename: Mazen
authors.initials: M
authors.lastname: El Alwani
authors.forename: Julnar
authors.initials: J
authors.lastname: Usta
authors.forename: George
authors.initials: G
authors.lastname: Nemer
authors.forename: Marwan
authors.initials: M
authors.lastname: El Sabban
authors.forename: Michel
authors.initials: M
authors.lastname: Nasser
authors.forename: Hala
authors.initials: H
authors.lastname: Bitar
authors.forename: Ramzi
authors.initials: R
authors.lastname: Souki
authors.forename: Ghassan S
authors.initials: GS
authors.lastname: Dbaibo
authors.forename: Fadi F
authors.initials: FF
authors.lastname: Bitar
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D055572:Ceramidases; D005964:Glucosyltransferases / Q000378:metabolism; D006400:Hematocrit; D000860:Hypoxia / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism
chemical_list: D013107:Sphingolipids; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase; D000581:Amidohydrolases; D055572:Ceramidases