Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List

Full text of this paper is not available in the ETD Center. Copies may be available for inter-library loan from University of Cincinnati or may be available for purchase from Proquest/UMI

ETD Abstract Container

Abstract Header

MEDIATION OF NICKEL-INDUCED ACUTE LUNG INJURY BY NITRIC OXIDE

McDowell, Susan Ann
http://rave.ohiolink.edu/etdc/view?acc_num=ucin999025181

Abstract Details

2001, PhD, University of Cincinnati, Medicine : Environmental Health Sciences.
Acute lung injury is a common, severe respiratory syndrome that can develop from indirect and direct insults to the lung. Despite extensive research since the initial description of acute lung injury over 30 years ago, questions remain about the basic pathogenic mechanisms and their relationship to therapeutic strategies. Microarray analysis during the progression of nickel-induced acute lung injury revealed an overall pattern of gene expression consistent with several pathogenic processes, including oxidative stress. NO can generate oxidative stress, either alone or by the formation of other reactive nitrogen species with reactive oxygen species. NO synthesis can be inhibited by binding of hepatocyte growth factor-like protein to the receptor tyrosine kinase Ron. Mice with a targeted deletion of the tyrosine kinase domain of Ron (Ron tk-/-) overproduce NO in response to endotoxin, therefore, these mice were used to examine whether the overproduction of NO would increase susceptibility to nickel-induced acute lung injury. In response to nickel, Ron tk-/- mice displayed decreased survival time, accelerated cytokine expression, augmented serum nitrite levels, and earlier onset of perivascular edema. To examine whether inhibiting NO would increase resistance to nickel-induced acute lung injury, NO synthesis was inhibited using NG-nitro-L-arginine methyl ester (L-NAME). Sixty-percent of L-NAME treated mice survived nickel-induced acute lung injury versus 5% of saline-treated mice. L-NAME treatment attenuated cytokine expression, polymorphonuclear cell infiltration and protein levels in lavage, and restored cyclin dependent kinase like 2 (Cdkl2) and surfactant gene expression. Restoration of surfactant gene expression is consistent with enhanced survival and attenuation of cytokine expression. These findings indicate that Ron is a key regulator of NO during nickel-induced acute lung injury and that NO inhibition may be protective by restoration of surfactant gene expression.
George Leikauf (Advisor)
NICKEL; ACUTE LUNG INJURY; RON; CDNA MICROARRAY

Recommended Citations

Citations

  • McDowell, S. A. (2001). MEDIATION OF NICKEL-INDUCED ACUTE LUNG INJURY BY NITRIC OXIDE [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin999025181

    APA Style (7th edition)

  • McDowell, Susan. MEDIATION OF NICKEL-INDUCED ACUTE LUNG INJURY BY NITRIC OXIDE. 2001. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin999025181.

    MLA Style (8th edition)

  • McDowell, Susan. "MEDIATION OF NICKEL-INDUCED ACUTE LUNG INJURY BY NITRIC OXIDE." Doctoral dissertation, University of Cincinnati, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin999025181

    Chicago Manual of Style (17th edition)

ucin999025181
© 2001, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.