Abstract

and specific aims): Alveolar macrophage (AM) functions involved in antimicrobial activity, including the respiratory burst (stimulated superoxide production), are altered by exposure to oxidants. The hypothesis is that sublethal oxidative stress alters the respiratory burst through two processes: a) modulation of Ca2+-dependent components of signal transduction by ROOH; and b) formation of adducts to components of signaling and/or the NADPH oxidase by 4-hydroxynonenal (4-HNE).
The specific aims are: 1) to determine the mechanism(s) whereby the changes in [Ca2+]i caused by ROOH alter signal transduction for the respiratory burst by measuring the Ca2+-dependent protein kinase C (alpha and beta forms), protein phosphatase 2B, and phospholipase D activities and phosphorylation of p47phox (a component of the respiratory burst oxidase); 2) to determine the source(s) of ROOH-inducible release of [Ca2+]i which differs from the IP3-sensitive pool released during ADP stimulation; and 3) to examine the mechanism(s) of alteration of the respiratory burst by 4-HNE by assessing the potential for direct alteration of NADPH oxidase components or components of signal transduction.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL037556-13
Application #
6030556
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1986-04-01
Project End
2001-06-30
Budget Start
1999-08-01
Budget End
2001-06-30
Support Year
13
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Forman, Henry Jay (2016) Redox signaling: An evolution from free radicals to aging. Free Radic Biol Med 97:398-407
Soñanez-Organis, José G; Peregrino-Uriarte, Alma B; Sotelo-Mundo, Rogerio R et al. (2011) Hexokinase from the white shrimp Litopenaeus vannamei: cDNA sequence, structural protein model and regulation via HIF-1 in response to hypoxia. Comp Biochem Physiol B Biochem Mol Biol 158:242-9
Forman, Henry Jay (2010) Reactive oxygen species and alpha,beta-unsaturated aldehydes as second messengers in signal transduction. Ann N Y Acad Sci 1203:35-44
Forman, Henry Jay; Maiorino, Matilde; Ursini, Fulvio (2010) Signaling functions of reactive oxygen species. Biochemistry 49:835-42
Cruz, Cristiane M; Rinna, Alessandra; Forman, Henry Jay et al. (2007) ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J Biol Chem 282:2871-9
Forman, Henry Jay (2007) Use and abuse of exogenous H2O2 in studies of signal transduction. Free Radic Biol Med 42:926-32
Liu, Honglei; Zhang, Hongqiao; Forman, Henry Jay (2007) Silica induces macrophage cytokines through phosphatidylcholine-specific phospholipase C with hydrogen peroxide. Am J Respir Cell Mol Biol 36:594-9
Liu, Honglei; Zhang, Hongqiao; Iles, Karen E et al. (2006) The ADP-stimulated NADPH oxidase activates the ASK-1/MKK4/JNK pathway in alveolar macrophages. Free Radic Res 40:865-74
Rinna, Alessandra; Torres, Martine; Forman, Henry Jay (2006) Stimulation of the alveolar macrophage respiratory burst by ADP causes selective glutathionylation of protein tyrosine phosphatase 1B. Free Radic Biol Med 41:86-91
Rahman, Irfan; Biswas, Saibal K; Jimenez, Luis A et al. (2005) Glutathione, stress responses, and redox signaling in lung inflammation. Antioxid Redox Signal 7:42-59

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