Photooxidative Damage in Cell Membranes
{'Code': '08060200', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'DCB', 'LongName': 'Division of Cellular Biosciences'}}
{'SignBlockName': 'Maryanna P. Henkart', 'PO_EMAI': None, 'PO_PHON': None}
Cell membranes are subject to structural and functional damage                  when irradiated in the presence of photosensitizing pigments.  A                prominent form of such damage is lipid peroxidation, which can                  result in altered fluidity, increased permeability, and other                   effects.  Photosensitized lipid peroxidation in biological                      systems has not been well studied in terms of reaction pathways,                cytotoxic effects, and protective/repair mechanisms.  The overall               objective of this research is to improve our understanding of                   membrane lipid peroxidation in each of these areas.  A                          comprehensive and diversified program of work is planned, using                 model systems initially (liposomes, erythrocyte membranes) and                  then cultured cells (murine L1210 cells).  The sensitizers of                   interest are non-bound uroporphyrin, and membrane-bound                         protoporphyrin and hematoporphyrin derivative (HPD).  Model                     Studies:  (a) Extensive work is planned involving cholesterol                   (Ch) as an in situ probe of Type I (free radical) vs Type II                    (singlet oxygen) pathways of lipid peroxidation.  (b)                           Amplification of photoinitiated lipid peroxidation by ascorbate                 will be investigated from a system-oriented perspective, e.g.                   effects of hydrogen peroxide and oxyradicals.  (c) Long-range                   peroxidation (with sensitizer and target lipid in separate                      membrane compartments) will be studied for the first time.  (d)                 Reductive metabolism (detoxification) of photoperoxides will be                 examined, using the glutathione reductase/peroxidase system.                    Cell Studies:  (a)  The first experiments to exploit Ch as a                    mechanistic probe in living cells will be carried out using (14C-               Ch in HPD-sensitized L1210 cells.  (b) The relationship between                 photoperoxidation and cytolethality will be investigated by (i)                 comparing lipid peroxide content and survivability, and (ii)                    determining how depletion of glutathione or glutathione                         peroxidase affects photosensitivity.                                                                                                                            The biochemical mechanisms and effects of lipid peroxidation on                 the integrity and function of biological membranes is of very                   great fundamental importance.  Information that will be derived                 from this research will have implications in enhancing our basic                knowledge of such diverse areas as the mechanisms by which light                interacts with photoreceptors, the mechanisms by which leukocytes               kill bacteria, and the reasons that cultured cells, when studied                under the light microscope for periods of time, may behave                      differently from cells in the organism.
{'FirstName': 'Albert', 'LastName': 'Girotti', 'PI_MID_INIT': 'W', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Albert W Girotti', 'EmailAddress': None, 'NSF_ID': '000104983', 'StartDate': '08/15/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Medical College of Wisconsin', 'CityName': 'MILWAUKEE', 'ZipCode': '532263548', 'PhoneNumber': '4149558563', 'StreetAddress': '8701 WATERTOWN PLANK RD', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Wisconsin', 'StateCode': 'WI', 'CONGRESSDISTRICT': '04', 'CONGRESS_DISTRICT_ORG': 'WI04', 'ORG_UEI_NUM': 'E8VWJXMMUQ67', 'ORG_LGL_BUS_NAME': 'THE MEDICAL COLLEGE OF WISCONSIN, INC.', 'ORG_PRNT_UEI_NUM': None}
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[{'Code': '1114', 'Text': 'Cellular Dynamics and Function'}, {'Code': '1117', 'Text': 'CELLULAR PHYSIOLOGY'}]
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8808227.xml'}