Interactions between neural membrane glycerophospholipid and sphingolipid mediators: a recipe for neural cell survival or suicide.
The neural membranes contain phospholipids, sphingolipids, cholesterol, and proteins. Glycerophospholipids and sphingolipids are precursors for lipid mediators involved in signal transduction processes. Degradation of glycerophospholipids by phospholipase A(2) (PLA(2)) generates arachidonic acid (AA) and docosahexaenoic acids (DHA). Arachidonic acid is metabolized to eicosanoids and DHA is metabolized to docosanoids. The catabolism of glycosphingolipids generates ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. These metabolites modulate PLA(2) activity. Arachidonic acid, a product derived from glycerophospholipid catabolism by PLA(2), modulates sphingomyelinase (SMase), the enzyme that generates ceramide and phosphocholine. Furthermore, sphingosine 1-phosphate modulates cyclooxygenase, an enzyme responsible for eicosanoid production in brain. This suggests that an interplay and cross talk occurs between lipid mediators of glycerophospholipid and glycosphingolipid metabolism in brain tissue. This interplay between metabolites of glycerophospholipid and sphingolipid metabolism may play an important role in initiation and maintenance of oxidative stress associated with neurologic disorders as well as in neural cell proliferation, differentiation, and apoptosis. Recent studies indicate that PLA(2) and SMase inhibitors can be used as neuroprotective and anti-apoptotic agents. Development of novel inhibitors of PLA(2) and SMase may be useful for the treatment of oxidative stress, and apoptosis associated with neurologic disorders such as stroke, Alzheimer disease, Parkinson disease, and head and spinal cord injuries.
Farooqui
Akhlaq A
AA
Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, Ohio 43210, USA.
Horrocks
Lloyd A
LA
Farooqui
Tahira
T
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002518:Ceramides / Q000502:physiology; D020404:Glycerophospholipids / Q000378:metabolism*; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy; D009474:Neurons / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D013107:Sphingolipids / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors
D002518:Ceramides; D020404:Glycerophospholipids; D013107:Sphingolipids; D016718:Arachidonic Acid; D010741:Phospholipases A; D013108:Sphingomyelin Phosphodiesterase