| Title |
Phosphorylation of FOXO3a by PI3K/Akt pathway in HK-2 renal proximal tubular epithelial cells exposed to cadmium
|
|---|---|
| Published in |
Archives of Toxicology, May 2013
|
| DOI | 10.1007/s00204-013-1077-6 |
| Pubmed ID | |
| Authors |
Kota Fujiki, Hisako Inamura, Masato Matsuoka |
| Abstract |
We examined the effects of cadmium chloride (CdCl2) exposure on the phosphorylation and function of the forkhead box class O (FOXO) transcription factor FOXO3a in HK-2 human renal proximal tubular cells. Phosphorylation of FOXO3a (at Thr32 and Ser253) and its upstream kinase, Akt (at Thr308 and Ser473) were markedly increased following exposure to 10 or 20 μM CdCl2. Treatment with wortmannin (500 nM), an inhibitor of phosphoinositide-3-kinase (PI3K), suppressed CdCl2-induced phosphorylation of Akt and FOXO3a at their Akt phosphorylation sites. CdCl2-induced phosphorylation of FOXO3a was markedly suppressed by the epidermal growth factor receptor inhibitor, AG1478 (1 μM), the Ca(2+)/calmodulin-dependent kinase II inhibitor, KN-93 (10 μM), and the Src inhibitor, PP2 (10 μM), but only partially suppressed by the insulin-like growth factor-1 receptor inhibitor, PPP (2.5 μM). Furthermore, the p38 inhibitor, SB203580 (20 μM), suppressed CdCl2-induced phosphorylation of Akt and FOXO3a, suggesting possible cross-talk between p38 mitogen-activated protein kinase and Akt. Although phosphorylation of FOXO3a was associated with reduced levels of nuclear FOXO3a, this change in cellular localization was transient. Silencing of FOXO3a expression using short interfering RNA suppressed CdCl2-induced cellular damage and accumulation of cytoplasmic nucleosomes in HK-2 cells. These results show that cadmium exposure induces phosphorylation of FOXO3a through the PI3K/Akt signaling pathway and suggest that FOXO3a phosphorylation (inactivation) transiently promotes survival of HK-2 cells. Phosphorylation of FOXO3a by the PI3K/Akt pathway may regulate cell fate in proximal tubules exposed to cadmium. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 17 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 41% |
| Researcher | 3 | 18% |
| Student > Master | 1 | 6% |
| Professor | 1 | 6% |
| Professor > Associate Professor | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 3 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 4 | 24% |
| Agricultural and Biological Sciences | 4 | 24% |
| Medicine and Dentistry | 2 | 12% |
| Environmental Science | 1 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 5 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 June 2014.
All research outputs
#20,231,820
of 22,757,541 outputs
Outputs from Archives of Toxicology
#2,359
of 2,632 outputs
Outputs of similar age
#170,049
of 194,981 outputs
Outputs of similar age from Archives of Toxicology
#18
of 20 outputs
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