Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.4.3.13 (
lysyl oxidase
)
1,248
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
TGF-beta1 induces differentiation and total inhibition of cardiac MyoFb cell division and DNA synthesis. These effects of TGF-beta1 are irreversible. Inhibition of MyoFb proliferation is accompanied with the expression of Smad1, Mad1, p15Ink4B and total inhibition of telomerase activity. Surprisingly, TGF-beta1-activated MyoFbs are growth-arrested not only at G1-phase but also at S-phase of the cell cycle. Staining with TUNEL indicates that these cells carry DNA damages. However, the absolute majority of MyoFbs are non-apoptotic cells as established with two apoptosis-specific methods, flow cytometry and caspase-dependent cleavage of
cytokeratin 18
. Expression in MyoFbs of proliferative cell nuclear antigen even in the absence of serum confirms that these MyoFbs perform repair of DNA damages. These results suggest that TGF-beta1-activated MyoFbs can be growth-arrested by two checkpoints, the G1/S checkpoint, which prevents cells from entering S-phase and the intra-S checkpoint, which is activated by encountering DNA damage during the S phase or by unrepaired damage that escapes the G1/S checkpoint. Despite carrying of the DNA damages TGF-beta1-activated MyoFbs are highly functional cells producing
lysyl oxidase
and contracting the collagen matrix.
...
PMID:TGF-beta1-induced cardiac myofibroblasts are nonproliferating functional cells carrying DNA damages. 1829 3
