alexa Cadmium induced p53-dependent activation of stress signaling, accumulation of ubiquitinated proteins, and apoptosis in mouse embryonic fibroblast cells.
Toxicology

Toxicology

Journal of Drug Metabolism & Toxicology

Author(s): Yu X, Sidhu JS, Hong S, Robinson JF, Ponce RA, , Yu X, Sidhu JS, Hong S, Robinson JF, Ponce RA,

Abstract Share this page

Abstract The tumor suppressor oncoprotein, p53, is a critical regulator of stress-induced growth arrest and apoptosis. p53 activity is regulated through the ubiquitin proteasome system (UPS) with stress-induced disruption leading to increased accumulation of p53, resulting in growth arrest. In the present study, we investigate the role of p53 to determine sensitivity to cadmium (Cd) and whether induction of stress signaling responses and perturbation of the UPS are involved in Cd-induced cytotoxicity and apoptosis. We treated synchronously cultured p53 transgenic mouse embryonic fibroblasts, both wild-type p53+/+ and knockout p53-/- cells, with cadmium chloride (Cd, 0.5-20μM) for 24 h. Cd-induced cytotoxicity was assessed by cellular morphology disruption and neutral red dye uptake assay. Proteins in the stress signaling pathway, including p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK); ubiquitination, such as high-molecular weight of polyubiquitinated proteins (HMW-polyUb); and apoptotic pathways, were all measured. We found that Cd induced p53-dependent cytotoxicity in the p53+/+ cells, which exhibited a twofold greater sensitivity. We observed a dose-dependent stimulation of p38 MAPK and SAPK/JNK phosphorylation that corresponded to accumulation of HMW-polyUb conjugates and lead to the induction of apoptosis, as evidenced by the elevation of cleaved caspase-3. Our study suggests that Cd-mediated cytotoxicity and induction of stress signaling responses, elevated accumulation of HMW-polyUb conjugates, and resulting apoptosis are all dependent on p53 status.
This article was published in Toxicol Sci and referenced in Journal of Drug Metabolism & Toxicology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords