Abstract

The proposed project uses a cultured myocardial cell system to study both the normal differentiation and induced hypertrophy of myocardial cells. Both processes involve alteration in the expression of specific genes which both reflect, and cause changes in the differentiation state of the myocardial cell. Little is known about how the intrinsic and extrinsic signals which induce these differentiative changes are transduced to the genes themselves to bring about alteration of their expression. The proposed experiments will address this question in two ways: First, to use DNA-mediated transfer of cloned cardiac-regulated genes into cultured myocardial cells to determine DNA sequence elements of the genes which respond to; normal differentiative signals and ultimately hypertrophic signals. Second, extrinsic signals (such as norepinephrine) which are now known to induce myocardial cell hypertrophy will be investigated as to the cellular mechanism(s) by which they bring about changes in the expression of specific genes, such as cardiac-regulated genes. It is expected that this dual approach will facilitate elucidation of the cellular pathways by which both normal and abnormal differentiative signals are transduced to the genes to bring about altered myocardial differentiation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL035561-02
Application #
3349563
Study Section
(SRC)
Project Start
1985-09-30
Project End
1988-09-29
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Kun, Ernest; Kirsten, Eva; Bauer, Pal I et al. (2006) Quantitative correlation between cellular proliferation and nuclear poly (ADP-ribose) polymerase (PARP-1). Int J Mol Med 17:293-300
Bauer, Pal I; Kirsten, Eva; Kun, Ernest (2005) Mechanisms of antitumor action of methyl-3,5-diiodo-4-(4'-methoxyphenoxy)benzoate: drug-induced protein dephosphorylations and inhibition of the permissive action of ceramide on growth factor induced cell proliferation. Oncol Rep 13:465-8
Bauer, Pal I; Kenesi, Erzsebet; Mendeleyev, Jerome et al. (2005) The influence of ATP on poly(ADP-ribose) metabolism. Int J Mol Med 16:321-4
Huang, Kai; Tidyman, William E; Le, Kim-Uyen T et al. (2004) Analysis of nucleotide sequence-dependent DNA binding of poly(ADP-ribose) polymerase in a purified system. Biochemistry 43:217-23
Kun, Ernest; Kirsten, Eva; Mendeleyev, Jerome et al. (2004) Regulation of the enzymatic catalysis of poly(ADP-ribose) polymerase by dsDNA, polyamines, Mg2+, Ca2+, histones H1 and H3, and ATP. Biochemistry 43:210-6
Kirsten, Eva; Kun, Ernest; Mendeleyev, Jerome et al. (2004) Activity assays for poly-ADP ribose polymerase. Methods Mol Biol 287:137-49
Tidyman, William E; Sehnert, Amy J; Huq, Anja et al. (2003) In vivo regulation of the chicken cardiac troponin T gene promoter in zebrafish embryos. Dev Dyn 227:484-96
Kun, Ernest; Kirsten, Eva; Ordahl, Charles P (2002) Coenzymatic activity of randomly broken or intact double-stranded DNAs in auto and histone H1 trans-poly(ADP-ribosylation), catalyzed by poly(ADP-ribose) polymerase (PARP I). J Biol Chem 277:39066-9
Butler, A J; Ordahl, C P (1999) Poly(ADP-ribose) polymerase binds with transcription enhancer factor 1 to MCAT1 elements to regulate muscle-specific transcription. Mol Cell Biol 19:296-306
Dockter, J L; Ordahl, C P (1998) Determination of sclerotome to the cartilage fate. Development 125:2113-24

Showing the most recent 10 out of 32 publications