+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Activin A-induced HepG2 liver cell apoptosis: involvement of activin receptors and smad proteins

, : Activin A-induced HepG2 liver cell apoptosis: involvement of activin receptors and smad proteins. Endocrinology 141(3): 1263-1272

A balance between cell proliferation and apoptosis is important for regulating normal liver function. Proteins of the transforming growth factor-beta superfamily are known to be important mediators of apoptosis in the liver. In this study we demonstrate that activin A potently induces apoptotic cell death in a hepatoma cell line, HepG2 cells. To determine the roles of activin receptors and downstream signaling proteins in activin A-induced apoptosis in these cells, the activin signaling pathway was analyzed using the transcription of an activin-responsive reporter gene, p3TP-Lux, as an assay. Although individual activin receptors had little effect on transcriptional activity, coexpression of an activin type I receptor and a type II receptor significantly increased both basal and activin-induced transcriptional activation, with the combination of receptors IB and IIB being the most potent. Similarly, expression of individual Smad proteins had only a modest effect on reporter gene activity, but the combination of Smad2 and Smad4 strongly stimulated transcription. Activin signaling induced a rapid relocation of Smad2 to the nucleus, as determined using a green fluorescence protein-Smad2 fusion protein. In contrast, green fluorescence protein-Smad4 remained localized to the cytoplasm unless it was coexpressed with Smad2. In agreement with the transcriptional response assays, overexpression or suppression of activin signaling components in HepG2 cells altered apoptosis. Overexpression of receptors IB and IIB or Smad proteins 2 and 4 stimulated apoptosis, whereas dominant negative mutant forms of the activin type IIB receptor or Smad2 blocked activin-stimulated apoptosis. These studies suggest that signaling from the cell surface to the nucleus through Smad proteins is a required component of the activin A-induced cell death process in liver cells.


PMID: 10698204

DOI: 10.1210/endo.141.3.7361

Other references

Gorelik, G.; Fang,; Wu, A., 2007: Impaired T Cell Protein Kinase C Activation Decreases ERK Pathway Signaling in Idiopathic and Hydralazine-Induced Lupus. Journal of Immunology 179(8): 53-63

Kinhikar, R.A., 2008: Does the fluence map editing in electronic tissue compensator improve dose homogeneity in bilateral field plan of head and neck patients?. The purpose of this study was to evaluate the effect of fluence map editing in electronic tissue compensator (ETC) on the dose homogeneity for head and neck cancer patients. Treatment planning using 6-MV X-rays and bilateral field arrangement empl...

Chandra, S.; Srivastava, M., 2003: Pteridology in the new millennium. NBRI Golden Jubilee Volume. This volume is a collection of 33 papers that provide information on the different research on Indian pteridophytes on areas such as systematics, morphology, anatomy, cytology, ecology, floristics, phytoremediation, economic utility, reproductive...

Bosch, X.; Mirapeix, E.; Font, J.; López-Soto, A.; Rodríguez, R.; Vivancos, J.; Revert, L.; Ingelmo, M.; Urbano-Márquez, A., 1994: Neutrophil anticytoplasmic antibodies: their diagnostic utility in vasculitis and glomerulonephritis. The prevalence and diagnostic usefulness of antineutrophil cytoplasmic antibodies (ANCA) were analyzed in a series of patients with different types of vasculitis, connective tissue diseases, nephropathies and lung diseases. Six hundred seventy-six...

Maddock T.H., 1972: The lesser long eared bat nyctophilus geoffroyi cave dweller or occasional visitor. South Australian Naturalist 46(4): 63-64

Zhang, Q.; Vo, N.; Goodman, R.H., 2000: Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB. A CREB-CREB binding protein (CBP) complex was used as bait to screen a mouse embryo cDNA library in yeast. One of the strongest interactions identified the histone binding protein RbAp48. RbAp48 also interacted weakly with CBP alone but did not in...

Archer, L.J.; Landman, O.E., 1969: Transport of donor deoxyribonucleic acid into the cell interior of thymine-starved Bacillus subtilis with chromosomes arrested at the terminus. The chromosomes of a tryptophan(-), thymine(-) double auxotroph of Bacillus subtilis were uniformly aligned at the chromosome terminus by an amino acid starvation treatment. By subsequent incubations, the starved culture was rendered competent, wh...

Mangnall, J.R., 1977: The organisation of marketing horticultural products. Wattie Industries has three main divisions: Cropper-NRM, General Foods Corporation, and J. Wattie Canneries. All are involved in the marketing of horticultural products. In J. Wattie Canneries there is particular emphasis on the processing and mar...

Chen, H-C.; Huang, H-J.; Wu, C-Y.; Lin, T-S.; Fang, H-Y., 2006: Esophageal schwannoma with tracheal compression. An esophageal schwannoma was found in a 73-year-old woman with cough, exertional dyspnea, and progressive dysphagia. Chest imaging showed an upper mediastinal mass (apex, right thoracic cavity) with direct lower tracheal compression. Esophagograph...

Anonymous, 1970: Apercu sur la helminthologique Sud-Vietnam. Rapp Pasteur Viet-Nam: 3-10