Document Detail

Hexavalent chromium induces energy metabolism disturbance and p53-dependent cell cycle arrest via reactive oxygen species in L-02 hepatocytes.
MedLine Citation:
PMID:  22886373     Owner:  NLM     Status:  Publisher    
Hexavalent chromium [Cr(VI)] has become a non-negligible pollutant in the world. Cr(VI) exposure leads to severe damage to the liver, but the mechanisms involved in Cr(VI)-mediated toxicity in the liver are unclear. The present study aimed to explore whether Cr(VI) induces energy metabolism disturbance and cell cycle arrest in human L-02 hepatocytes. We showed that Cr(VI) inhibited state 3 respiration, respiratory control rate (RCR), and subsequently induced energy metabolism disturbance with decreased ATP production. Interestingly, cell cycle analysis by flow cytometry and protein expression analysis by western blotting revealed that low dose of Cr(VI) (4 uM) exposure induced S phase cell cycle arrest with decreased mediator of replication checkpoint 1 (Mrc1) and cyclin-dependent kinase 2 (CDK2), while higher doses of Cr(VI) (16, 32 uM) exposure resulted in G2/M phase arrest with decreased budding uninhibited by benzimidazoles-related 1 (BubR1) and cell division cycle 25 (CDC25). Mechanism study revealed that Cr(VI) decreased the activities of mitochondrial respiratory chain complex (MRCC) I and II, thus leading to ROS accumulation. Moreover, inhibiting ROS production by antioxidant N-acetyl-L: -cysteine (NAC) rescued Cr(VI)-induced ATP depletion and cell cycle arrest. ROS-mediated p53 activation was found to involve in Cr(VI)-induced cell cycle arrest, and p53 inhibitor Pifithrin-α (PFT-α) rescued Cr(VI)-induced reduction of check point proteins Mrc1 and BubR1, thus inhibiting cell cycle arrest. In summary, the present study provides experimental evidence that Cr(VI) leads to energy metabolism disturbance and p53-dependent cell cycle arrest via ROS in L-02 hepatocytes.
Fang Xiao; Xiaotao Feng; Ming Zeng; Lan Guan; Qingqing Hu; Caigao Zhong
Related Documents :
15837063 - How to make a placenta: mechanisms of trophoblast cell differentiation in mice--a review.
22898083 - Caveolin-1 knockdown is associated with the metastasis and proliferation of human lung ...
23022133 - Uptake, efflux, and mass transfer coefficient of fluorescent pamam dendrimers into panc...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-11
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  -     ISSN:  1573-4919     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Health Toxicology, School of Public Health, Central South University, Changsha, 410078, People's Republic of China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Modeling loop backbone flexibility in receptor-ligand docking simulations.
Next Document:  " . . . There is No War Here; It is Only the Relationship That Makes Us Scared": Factors Having an I...