Oxygen plays a vital role in energy metabolism and immune defense in mammals, and it works within a narrow physiological range. The oxygen sensing mechanism enables mammalian cells to utilize oxygen effectively, defending against hypoxia as well as oxidative stress. Although the mechanism is poorly understood at the present, there is circumstantial evidence for a universal oxygen sensor inside cells. This research proposal aims to contribute to our knowledge on this topic by cloning and characterizing the human oxygen sensor. Biochemical approaches will be used to purify this sensory protein, a NAD(P)H oxidase on plasma membrane, and the cDNA will be cloned (Specific Aim 1). In vitro assays will he carried out to determine biochemical properties of the purified protein (Specific Aim 2) and in vivo studies at cellular and molecular levels will be performed on wild type oxygen sensor and its gain of function mutations, examining the downstream effect on hypoxia-regulated Epo gene expression (Specific Aim 3). A detailed understanding of the oxygen sensor will provide insights into the oxygen sensing pathway.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK009678-01
Application #
2414752
Study Section
Special Emphasis Panel (ZRG4-HEM-2 (01))
Program Officer
Bishop, Terry Rogers
Project Start
1998-02-10
Project End
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Zhu, H; Qiu, H; Yoon, H W et al. (1999) Identification of a cytochrome b-type NAD(P)H oxidoreductase ubiquitously expressed in human cells. Proc Natl Acad Sci U S A 96:14742-7