Prostaglandins of J series control heme oxygenase expression: potential significance in modulating neuroinflammation.
Cyclopentenone prostaglandins (cyPGs) are a subfamily of prostaglandins that are characterized by the cyclopentenone ring in their structure. They exert their effect after active transportation into the cell, probably by interacting with cellular target proteins or DNA sequences. The cyPGs have anti-inflammatory activities, especially important during the resolution of inflammation, anticancer, and cytoprotective properties. Here, we show that the cyPGs, especially the 15-deoxy-Delta(12,14) PGJ(2), can specifically induce heme oxygenase 1 in mouse primary neuronal cells. Heme oxygenase is the enzyme responsible for the degradation of heme into biliverdin, ferrous iron, and carbon monoxide. This enzyme conveys protection to oxidative cellular injury by degrading the pro-inflammatory heme; producing biliverdin and bilirubin, potent antioxidants; producing carbon monoxide, a neurotransmitter that also has anti-inflammatory and vasodilatory properties; and assisting in keeping iron cellular homeostasis. CyPGs appear to possess a promising future in designing therapeutics for many neurologic diseases, such as Alzheimer's disease, vascular-related dementia, multiple sclerosis, ischemic conditions, and many others in which inflammation is a part of the pathophysiology.
Zhuang
Hean
H
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Kim
Yun-Sook
YS
Namiranian
Khodadad
K
Doré
Sylvain
S
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D008565:Membrane Proteins; D051379:Mice; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors
D008565:Membrane Proteins; C037112:9-deoxy-delta-9-prostaglandin D2; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D015230:Prostaglandin D2