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Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytesWe have shown that a combination of fish oil (high in n-3 fatty acids) with the butyrate-producing fiber pectin, upregulates apoptosis in colon cells exposed to the carcinogen azoxymethane, protecting against colon tumor development. We now hypothesize that n-3 fatty acids prime the colonocytes such that butyrate can initiate apoptosis. To test this, 30 Sprague-Dawley rats were provided with diets differing in the fatty acid composition (corn oil, fish oil or a purified fatty acid ethyl ester diet). Intact colon crypts were exposed ex vivo to butyrate, and analyzed for reactive oxygen species (ROS), mitochondrial membrane potential (MMP), translocation of cytochrome C to the cytosol, and caspase-3 activity (early events in apoptosis). The fatty acid composition of the three major mitochondrial phospholipids was also determined, and an unsaturation index calculated. The unsaturation index in cardiolipin was correlated with ROS levels (R = 0.99; P = 0.02). When colon crypts from fish oil and FAEE-fed rats were exposed to butyrate, MMP decreased (P = 0.041); and translocation of cytochrome C to the cytosol (P = 0.037) and caspase-3 activation increased (P = 0.032). The data suggest that fish oil may prime the colonocytes for butyrate-induced apoptosis by enhancing the unsaturation of mitochondrial phospholipids, especially cardiolipin, resulting in an increase in ROS and initiating apoptotic cascade.
Document ID
20040088005
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Hong, Mee Young
(College Station TX 77843-2471, United States)
Chapkin, Robert S.
Barhoumi, Rola
Burghardt, Robert C.
Turner, Nancy D.
Henderson, Cara E.
Sanders, Lisa M.
Fan, Yang-Yi
Davidson, Laurie A.
Murphy, Mary E.
Spinka, Christine M.
Carroll, Raymond J.
Lupton, Joanne R.
Date Acquired
August 21, 2013
Publication Date
November 1, 2002
Publication Information
Publication: Carcinogenesis
Volume: 23
Issue: 11
ISSN: 0143-3334
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: P30-ES-09106
CONTRACT_GRANT: CA 59034
CONTRACT_GRANT: CA 82907
CONTRACT_GRANT: CA 61750
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Radiation Health

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