Abstract

Apoptosis is the name of the stereotyped program by which cells commit suicide. It is characterized by destruction of chromatin and degradation of the DNA, usually to nucleosomal fragments, accompanied by cell shrinkage and loss of cell substance through blabbing. Apoptosis is of wide physiological and pathological significance, important in embryogenesis, control of tissue growth and the regulation of the immune system, as well as in the elimination of cells that have sustained serious damage, particularly to their genomes. The Investigators have shown that in several lines of cells exposed to a variety of apoptosis-inducing agents, apoptosis with its accompanying genome destruction is preceded by intracellular acidification, and that the genome is preserved if this acidification is prevented. They propose to investigate the mechanism of acidification in cells undergoing apoptosis, and to study a ubiquitous acid endonuclease that may be responsible for the degradation of DNA during the apoptosis program.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG013501-02
Application #
2330220
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Finkelstein, David B
Project Start
1996-02-10
Project End
2001-01-31
Budget Start
1997-02-01
Budget End
1998-01-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Gustafsson, Asa B; Sayen, M Richard; Williams, Scott D et al. (2002) TAT protein transduction into isolated perfused hearts: TAT-apoptosis repressor with caspase recruitment domain is cardioprotective. Circulation 106:735-9
Gottlieb, R A (2001) Mitochondria and apoptosis. Biol Signals Recept 10:147-61
Gottlieb, R A; Adachi, S (2000) Nitrogen cavitation for cell disruption to obtain mitochondria from cultured cells. Methods Enzymol 322:213-21
Gottlieb, R A (2000) Role of mitochondria in apoptosis. Crit Rev Eukaryot Gene Expr 10:231-9
Mutomba, M C; Yuan, H; Konyavko, M et al. (2000) Regulation of the activity of caspases by L-carnitine and palmitoylcarnitine. FEBS Lett 478:19-25
Gottlieb, R A (1999) Mitochondria: ignition chamber for apoptosis. Mol Genet Metab 68:227-31
Adachi, S; Gottlieb, R A; Babior, B M (1998) Lack of release of cytochrome C from mitochondria into cytosol early in the course of Fas-mediated apoptosis of Jurkat cells. J Biol Chem 273:19892-4
Gottlieb, R A; Babior, B M (1997) Regulation of Fas-mediated apoptosis. Curr Top Cell Regul 35:69-105
Niessen, H; Meisenholder, G W; Li, H L et al. (1997) Granulocyte colony-stimulating factor upregulates the vacuolar proton ATPase in human neutrophils. Blood 90:4598-601
Adachi, S; Cross, A R; Babior, B M et al. (1997) Bcl-2 and the outer mitochondrial membrane in the inactivation of cytochrome c during Fas-mediated apoptosis. J Biol Chem 272:21878-82

Showing the most recent 10 out of 13 publications