The cytotoxic effect of bromoenol lactone, a calcium-independent phospholipase A2 inhibitor, on rat cortical neurons in culture.
This study characterized the phospholipase A(2) (PLA(2)) activity in cerebral cortex of fetal rat brain and investigated effects of chemical inhibition of Ca(2+)-independent PLA(2) (iPLA(2)) on neurite outgrowth and cell development of cortical neurons in vitro. The PLA(2) activity in fetal brain was insensitive to a Ca(2+)-chelator EGTA and was significantly impaired by an iPLA(2) inhibitor, bromoenol lactone (BEL). Following treatment with BEL, cortical neurons showed acute loss of neurites and impaired cell body, which were clearly dose- and time-dependent. Nuclear staining revealed nuclear regression (shrinkage), but not fragmentation, in BEL-treated cells. The cytotoxic effect of BEL was additive with arachidonic acid (AA) and AA alone also induced neurite demise. BEL treatment resulted in increased production of prostaglandin E(2). Overall data suggest that iPLA(2), a primary PLA(2) isoform in cerebral cortex, displays a housekeeping role in development and neurite outgrowth in cortical neurons in vitro probably via maintaining phospholipid membrane remodeling rather than generating free fatty acids and lysophospholipids.
Laboratory of Veterinary Physiology, Kitasato University School of Veterinary Medicine, Towada, Aomori 034-8628, Japan. kurusu@vmas.kitasato-u.ac.jp
Shiro
S
Kurusu
Kohtaro
K
Matsui
Toshimichi
T
Watanabe
Toshinobu
T
Tsunou
Mitsumori
M
Kawaminami
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D015232:Dinoprostone / Q000096:biosynthesis; D018698:Glutamic Acid / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D016501:Neurites; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D054512:Phospholipases A2, Calcium-Independent / Q000037:antagonists & inhibitors*; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D009281:Naphthalenes; D011753:Pyrones; D016718:Arachidonic Acid; D018698:Glutamic Acid; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D054512:Phospholipases A2, Calcium-Independent; D015232:Dinoprostone