Murine acyl-CoA binding protein : expression in transformed colon cells, structure, and function in microsomal phosphatidic acid biosynthesis /
Fatty acyl-CoAs affect many cellular functions and serve as cellular building blocks. Intestinal enterocytes contain at least three families of cytosolic proteins that may modulate the activities of fatty acyl-CoA: acyl-CoA binding protein (ACBP), fatty acid binding proteins (including liver, L-F...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1998.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=737704411&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Fatty acyl-CoAs affect many cellular functions and serve as cellular building blocks. Intestinal enterocytes contain at least three families of cytosolic proteins that may modulate the activities of fatty acyl-CoA: acyl-CoA binding protein (ACBP), fatty acid binding proteins (including liver, L-FABP and intestinal, I-FABP), and sterol carrier protein-2 (SCP-2). Immortalized rat colon epithelial cell lines expressed only ACBP and SCP-2 at levels of 0.75-+O.13 and 0.42-+O.02 ng/mg protein. Ras and src transformation increased colon cell density and differentially altered ACBP and SCP-2 expression without affecting I-FABP or L-FABP levels. ACBP levels were 1.8-fold and 1.5-fold increased in ras- and src-transformed cells, respectively. In contrast, SCP-2 expression was significantly decreased 55% and 67% in ras-and src-transfon-ned cells, respectively. Butyrate treatment of transformed cells decreased cell proliferation up to 60-85% and decreased ACBP expression in all cell lines, but had no effect on the levels of SCP-2, IFABP, or L-FABP. These studies suggest that the differential expression of ACBP and SCP-2 in rat colonic cell lines, as well as their modulation by butyrate, may be altered by cell transformation. Although acyl-CoA binding protein (ACBP) is found in high levels in tumorigenic cells, the molecular basis for the elevated levels of ACBP in malignant cells, ligand binding characteristics, and function in microsomal phospholipid synthesis have not been resolved. To address whether tumorigenic ACBP differs from the native protein, ACBP was purified from LM cell fibroblasts, and its primary structure examined by delayed extraction MALDI-Linear TOF mass spectrometry. ACBP from LM cells was identical to native mouse ACBP. Furthermore, mouse and rat ACBP enhanced microsomal phosphatidic acid formation and protected oleoyl-CoA against hydrolysis. Mouse ACBP also inhibited microsomal phospholipid acyl chain remodeling of choline containing phospholipids, phosphatidylcholine and sphingomyelin, by 50% and 64%, respectively. These effects were specific as compared to those of native rat liver or recombinant rat ACBP. Finally, mouse and rat ACBP shifted the incorporation of oleoyl-CoA from microsomal phospholipid acyl chain remodeling to phosphatidic acid biosynthesis. These data show a role for murine ACBPs in regulating microsomal phosphatidic acid biosynthesis and acyl chain remodeling in vitro. |
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| Item Description: | Vita. "Major Subject: Veterinary Pathology". |
| Physical Description: | ix, 76 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references: pages 62-73. |