RGD Reference Report - SMAD proteins are involved in apoptosis induction in ventricular cardiomyocytes. - Rat Genome Database

RGD Reference Report - SMAD proteins are involved in apoptosis induction in ventricular cardiomyocytes. - Rat Genome Database

Submit Data | Help | Video Tutorials | News | Publications | Download | REST API | Citing RGD | Contact

General

SMAD proteins are involved in apoptosis induction in ventricular cardiomyocytes.
Authors:	Schneiders, Daniela Heger, Jacqueline Best, Patrick Michael Piper, Hans Taimor, Gerhild
Citation:	Schneiders D, etal., Cardiovasc Res. 2005 Jul 1;67(1):87-96. Epub 2005 Mar 23.
RGD ID:	12903280
Pubmed:	PMID:15949472 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.cardiores.2005.02.021 (Journal Full-text)
OBJECTIVE: The transcription factor AP-1 is a mediator of hypertrophic growth and apoptosis in cardiomyocytes. This puts AP-1 in the center of two important processes found in the failing heart and implies that variations (i) in the AP-1 composition itself or (ii) in additional, interacting transcription factors are responsible for the diverse actions of AP-1. To test this hypothesis, we performed studies on isolated ventricular cardiomyocytes of rat under hypertrophy- or apoptosis-inducing conditions. METHODS AND RESULTS: The NO donor SNAP (100 microM), which is a pro-apoptotic stimulus in cardiomyocytes, activated AP-1 within 2 h. c-Jun, JunB and FosB are identified as the main components of this AP-1 complex. This complex formation is identical to the composition of AP-1 found under hypertrophic growth stimulation by phenylephrine (PE, 10 muM). Analysis of other transcription factors able to interact with AP-1 revealed activation of SMAD activity only during stimulation with SNAP to 131+/-9.6% (p < 0.05 vs. control, n = 9). The SMAD complex is formed from SMAD4 and 3. Intracellular scavenging of SMAD proteins by transformation of cardiomyocytes with SMAD decoy oligonucleotides or inhibition of SMAD4 synthesis using SMAD4 antisense oligonucleotides reduced the number of apoptotic cells under stimulation with SNAP from 13.3 +/- 1.2% to control levels (8 +/- 1%, p < 0.05, n = 6). TGFbeta, which is a known stimulator of SMAD proteins, is also shown to stimulate apoptosis in cardiomyocytes. Again, simultaneous activation of AP-1 and SMAD is needed for this apoptosis induction. CONCLUSIONS: In conclusion, AP-1/SMAD signaling has been identified as a common pathway in cardiomyocyte apoptosis. In contrast, SMAD proteins are dispensable for AP-1-mediated hypertrophic growth. This finding characterizes SMAD proteins as potential candidates for proteins that shift AP-1 signaling from hypertrophy to apoptosis.

Gene Ontology Annotations Click to see Annotation Detail View

Biological Process

Only show annotations with direct experimental evidence (0 objects hidden)

Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
positive regulation of cardiac muscle cell apoptotic process		IMP		12903280		RGD

Objects Annotated

Genes (Rattus norvegicus)

Smad4 (SMAD family member 4)

Additional Information