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The Cytotoxic Effect of Bromoenol Lactone, a Calcium-independent Phospholipase A2 Inhibitor, on Rat Cortical Neurons in Culture

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Abstract

This study characterized the phospholipase A2 (PLA2) activity in cerebral cortex of fetal rat brain and investigated effects of chemical inhibition of Ca2+-independent PLA2 (iPLA2) on neurite outgrowth and cell development of cortical neurons in vitro. The PLA2 activity in fetal brain was insensitive to a Ca2+-chelator EGTA and was significantly impaired by an iPLA2 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 E2. Overall data suggest that iPLA2, a primary PLA2 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.

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Acknowledgments

We thank Drs X. Wang (Massachusetts General Hospital, MA, USA) and A. Sapirstein (The Johns Hopkins University, MD, USA) for advices on experimental technique and Ms M. Nakata for assistance with manuscript preparation.

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Authors and Affiliations

  1. Laboratory of Veterinary Physiology, Kitasato University School of Veterinary Medicine, Towada, Aomori, 034-8628, Japan

    Shiro Kurusu, Kohtaro Matsui, Toshimichi Watanabe, Toshinobu Tsunou & Mitsumori Kawaminami

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  1. Shiro Kurusu
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  2. Kohtaro Matsui
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  3. Toshimichi Watanabe
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  4. Toshinobu Tsunou
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  5. Mitsumori Kawaminami
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Correspondence to Shiro Kurusu.

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Kurusu, S., Matsui, K., Watanabe, T. et al. The Cytotoxic Effect of Bromoenol Lactone, a Calcium-independent Phospholipase A2 Inhibitor, on Rat Cortical Neurons in Culture. Cell Mol Neurobiol 28, 1109–1118 (2008). https://doi.org/10.1007/s10571-008-9287-9

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  • DOI: https://doi.org/10.1007/s10571-008-9287-9

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