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Antioxidative function of liver fatt...
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Yan, Jing.
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Antioxidative function of liver fatty acid binding protein .
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Antioxidative function of liver fatty acid binding protein ./
作者:
Yan, Jing.
面頁冊數:
203 p.
附註:
Source: Dissertation Abstracts International, Volume: 72-05, Section: B, page: .
Contained By:
Dissertation Abstracts International72-05B.
標題:
Biology, General. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR71126
ISBN:
9780494711262
Antioxidative function of liver fatty acid binding protein .
Yan, Jing.
Antioxidative function of liver fatty acid binding protein .
- 203 p.
Source: Dissertation Abstracts International, Volume: 72-05, Section: B, page: .
Thesis (Ph.D.)--University of Manitoba (Canada), 2010.
Liver fatty acid binding protein (L-FABP) binds and translocates many lipophilic substrates within the cytoplasm including long chain fatty acids. Moreover it was reported that L-FABP possesses antioxidative properties within hepatocytes. However, the mechanism of L-FABP's antioxidative activity remains to be determined.
ISBN: 9780494711262Subjects--Topical Terms:
1018625
Biology, General.
Antioxidative function of liver fatty acid binding protein .
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Source: Dissertation Abstracts International, Volume: 72-05, Section: B, page: .
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Thesis (Ph.D.)--University of Manitoba (Canada), 2010.
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Liver fatty acid binding protein (L-FABP) binds and translocates many lipophilic substrates within the cytoplasm including long chain fatty acids. Moreover it was reported that L-FABP possesses antioxidative properties within hepatocytes. However, the mechanism of L-FABP's antioxidative activity remains to be determined.
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Peroxisome proliferator activated receptor (PPAR) agonists and antagonists can regulate L-FABP levels. However, it needs to be investigated how PPAR agonists and antagonists regulate L-FABP expression. And whether the altered expression of L-FABP by these agents will affect its antioxidative properties within hepatocytes remains unclear. In this thesis we employed clofibrate (PPARalpha agonist), MK886 (PPARalpha antagonist), and GW9662 (PPARgamma antagonist) to elucidate the mechanism whereby PPAR regulate L-FABP expression and what effect such expression has on the antioxidant activity of L-FABP in CRL-1548 hepatoma cells. Clofibrate served to upregulate L-FABP expression while MK886 and GW9662 were employed to inhibit L-FABP expression. The principal findings revealed that clofibrate treatment enhanced L-FABP mRNA stability and transcription, which resulted in increased L-FABP levels, while MK866 and GW9662 reduced these levels. We also demonstrated that increases in L-FABP levels were associated with reduced cytosolic reactive oxygen species (ROS), while L-FABP siRNA knockdown resulted in a decrease in L-FABP expression and an associated increase in ROS levels.
520
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The antioxidant mechanism of recombinant rat L-FABP in the presence of a hydrophilic (AAPH) and lipophilic (AMVN) free radical generators was also evaluated. Recombinant rat L-FABP was produced in E. coli and its amino acid sequence was confirmed by MALDI QqTOF MS. Antioxidant activity was assayed using the thiobarbituric acid method. Ascorbic acid served as a positive control for the AAPH reaction while alpha-tocopherol was used as a positive control for the AMVN reaction. The antioxidant activity of recombinant L-FABP was greater when free radicals were generated with AAPH than AMVN. Oxidative modification of L-FABP included up to five methionine oxidative peptides with a total of 80 Da mass shift compared to native L-FABP. These findings suggest that the mechanism of L-FABP's antioxidant activity involved the reaction of methionine with free radicals.
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In conclusion, L-FABP expression is regulated by PPAR agonists and antagonists through transcription and mRNA stability. Moreover, methionine residues appear to play an important role in the antioxidative activity of L-FABP.
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School code: 0303.
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