Skip to Main Content
Frequently Asked Questions
Submit an ETD
Global Search Box
Need Help?
Keyword Search
Participating Institutions
Advanced Search
School Logo
Files
File List
case1180231149.pdf (4.91 MB)
ETD Abstract Container
Abstract Header
CLINICAL AND ANIMAL STUDIES OF LIPID-DERIVED PROTEIN MODIFICATIONS IN AUTISM, KIDNEY DIALYSIS, KERATITIS AND AGE-RELATED MACULAR DEGENERATION
Author Info
Lu, Liang
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=case1180231149
Abstract Details
Year and Degree
2007, Doctor of Philosophy, Case Western Reserve University, Chemistry.
Abstract
Lipid oxidation in diverse biological systems contributes to normal physiological processes and is increasingly believed to be associated with age-related diseases. Lipid oxidation products, e.g., isolevuglandins and ã-hydroxyalkenals, and their protein adducts are produced during and may even contribute to disease pathogenesis. This thesis reports clinical studies on the occurrence of 2-pentylpyrrole, iso[4]LGE2-protein adducts and carboxyethylpyrrole (CEP) protein modifications in brain and blood from autistic individuals, blood from hemodialysis patients, as well as cornea from a mouse model of keratitis. Similar levels of these modifications and autoantibodies against them were detected in blood from both autistic individuals and normal controls. Autistic patients born prematurely showed significantly elevated iso[4]LGE2-protein adduct levels. Oral supplementation with alpha tocopherol had no significant effect on levels of oxidative protein modifications in patients treated by hemodialysis, and thus, does not result in an antioxidant benefit in hemodialysis. We detected the formation of iso[4]LGE2- and LGE2-protein adducts upon injection of lipopolysaccharide into mouse cornea, a model of keratitis. We anticipated that docosahexaenoic acid-derived oxidatively truncated phospholipids containing reactive electrophilic 4-hydroxy-7-oxohept-5-enoates (HOHA) would convert the primary amino group of PEs into carboxyethylpyrrole phosphatidylethanolamine adducts (CEP-PEs). I detected a low level of CEP-PE in a bovine retinal lipid extract and quantified the generation of CEP-PE adduct and a CEP-modified lysophospholipid, lysoCEP-PE, upon UV light-promoted oxidation of the retinal lipid extract. Similar levels, about 1.2 ng/mL, of lysoCEP-PE were detected in plasma samples from a normal control and a patient with age-related macular degeneration (AMD). A reliable source of CEP-modified proteins was needed to provide: (1) reagents for immunoassays that measure levels of CEPs or anti-CEP autoantibodies as biomarkers for clinical prognosis of AMD, and (2) antigens to test the hypothesis that immune responses against CEP-protein adducts generated in the retina contribute to the pathogenesis of AMD, (3) for studies on the stimulation of angiogenesis by CEPs and its inhibition, and (4) for the production of CEP-PEs as standards for analyses of these potential markers of oxidative injury. An efficient, reliable synthesis of CEPs was developed that exploits a flourenylmethyl ester derivative of HOHA as a key reagent.
Committee
Robert Salomon (Advisor)
Subject Headings
Chemistry, Biochemistry
Keywords
doubly charged ion
;
CEPs
;
charged ion
;
LGE2
;
CH2
;
PROTEIN
Recommended Citations
Refworks
EndNote
RIS
Mendeley
Citations
Lu, L. (2007).
CLINICAL AND ANIMAL STUDIES OF LIPID-DERIVED PROTEIN MODIFICATIONS IN AUTISM, KIDNEY DIALYSIS, KERATITIS AND AGE-RELATED MACULAR DEGENERATION
[Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1180231149
APA Style (7th edition)
Lu, Liang.
CLINICAL AND ANIMAL STUDIES OF LIPID-DERIVED PROTEIN MODIFICATIONS IN AUTISM, KIDNEY DIALYSIS, KERATITIS AND AGE-RELATED MACULAR DEGENERATION.
2007. Case Western Reserve University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=case1180231149.
MLA Style (8th edition)
Lu, Liang. "CLINICAL AND ANIMAL STUDIES OF LIPID-DERIVED PROTEIN MODIFICATIONS IN AUTISM, KIDNEY DIALYSIS, KERATITIS AND AGE-RELATED MACULAR DEGENERATION." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1180231149
Chicago Manual of Style (17th edition)
Abstract Footer
Document number:
case1180231149
Download Count:
1,647
Copyright Info
© 2007, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.