Tags

Type your tag names separated by a space and hit enter

Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-кB, and AP-1 pathways in human endothelial cells.
Toxicology. 2015 Dec 02; 338:104-16.T

Abstract

Cadmium (Cd), a widespread cumulative pollutant, is a known human carcinogen, associated with inflammation and tumors. Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in tumor metastasis; however, the mechanisms underlying the MMP-9 expression induced by Cd remain obscure in human endothelial cells. Here, Cd elevated MMP-9 expression in dose- and time-dependent manners in human endothelial cells. Cd increased ROS production and the ROS-producing NADPH oxidase. Cd translocates p47(phox), a key subunit of NADPH oxidase, to the cell membrane. Cd also activated the phosphorylation of EGFR, Akt, Erk1/2, and JNK1/2 in addition to promoting NF-кB and AP-1 binding activities. Specific inhibitor and mutagenesis studies showed that EGFR, Akt, Erk1/2, JNK1/2 and transcription factors NF-κB and AP-1 were related to Cd-induced MMP-9 expression in endothelial cells. Akt, Erk1/2, and JNK1/2 functioned as upstream signals in the activation of NF-κB and AP-1, respectively. In addition, N-acetyl-l-cystein (NAC), diphenyleneiodonium chloride (DPI) and apocynin (APO) inhibited the Cd-induced activation of EGFR, Akt, Erk1/2, JNK1/2, and p38 MAPK, indicating that ROS production by NADPH oxidase is the furthest upstream signal in MMP-9 expression. At present, it states that Cd displayed marked invasiveness in ECV304 cells, which was partially abrogated by MMP-9 neutralizing antibodies. These results demonstrated that Cd induces MMP-9 expression via ROS-dependent EGFR->Erk1/2, JNK1/2->AP-1 and EGFR->Akt->NF-κB signaling pathways and, in turn, stimulates invasiveness in human endothelial cells.

Authors+Show Affiliations

Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea. Electronic address: ydjung@chonnam.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26514923

Citation

Lian, Sen, et al. "Cadmium Induces Matrix Metalloproteinase-9 Expression Via ROS-dependent EGFR, NF-кB, and AP-1 Pathways in Human Endothelial Cells." Toxicology, vol. 338, 2015, pp. 104-16.
Lian S, Xia Y, Khoi PN, et al. Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-кB, and AP-1 pathways in human endothelial cells. Toxicology. 2015;338:104-16.
Lian, S., Xia, Y., Khoi, P. N., Ung, T. T., Yoon, H. J., Kim, N. H., Kim, K. K., & Jung, Y. D. (2015). Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-кB, and AP-1 pathways in human endothelial cells. Toxicology, 338, 104-16. https://doi.org/10.1016/j.tox.2015.10.008
Lian S, et al. Cadmium Induces Matrix Metalloproteinase-9 Expression Via ROS-dependent EGFR, NF-кB, and AP-1 Pathways in Human Endothelial Cells. Toxicology. 2015 Dec 2;338:104-16. PubMed PMID: 26514923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-кB, and AP-1 pathways in human endothelial cells. AU - Lian,Sen, AU - Xia,Yong, AU - Khoi,Pham Ngoc, AU - Ung,Trong Thuan, AU - Yoon,Hyun Joong, AU - Kim,Nam Ho, AU - Kim,Kyung Keun, AU - Jung,Young Do, Y1 - 2015/11/11/ PY - 2015/09/03/received PY - 2015/10/17/revised PY - 2015/10/19/accepted PY - 2015/10/31/entrez PY - 2015/10/31/pubmed PY - 2016/3/8/medline KW - Cadmium KW - Cell invasion KW - Endothelial cells KW - MMP-9 SP - 104 EP - 16 JF - Toxicology JO - Toxicology VL - 338 N2 - Cadmium (Cd), a widespread cumulative pollutant, is a known human carcinogen, associated with inflammation and tumors. Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in tumor metastasis; however, the mechanisms underlying the MMP-9 expression induced by Cd remain obscure in human endothelial cells. Here, Cd elevated MMP-9 expression in dose- and time-dependent manners in human endothelial cells. Cd increased ROS production and the ROS-producing NADPH oxidase. Cd translocates p47(phox), a key subunit of NADPH oxidase, to the cell membrane. Cd also activated the phosphorylation of EGFR, Akt, Erk1/2, and JNK1/2 in addition to promoting NF-кB and AP-1 binding activities. Specific inhibitor and mutagenesis studies showed that EGFR, Akt, Erk1/2, JNK1/2 and transcription factors NF-κB and AP-1 were related to Cd-induced MMP-9 expression in endothelial cells. Akt, Erk1/2, and JNK1/2 functioned as upstream signals in the activation of NF-κB and AP-1, respectively. In addition, N-acetyl-l-cystein (NAC), diphenyleneiodonium chloride (DPI) and apocynin (APO) inhibited the Cd-induced activation of EGFR, Akt, Erk1/2, JNK1/2, and p38 MAPK, indicating that ROS production by NADPH oxidase is the furthest upstream signal in MMP-9 expression. At present, it states that Cd displayed marked invasiveness in ECV304 cells, which was partially abrogated by MMP-9 neutralizing antibodies. These results demonstrated that Cd induces MMP-9 expression via ROS-dependent EGFR->Erk1/2, JNK1/2->AP-1 and EGFR->Akt->NF-κB signaling pathways and, in turn, stimulates invasiveness in human endothelial cells. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/26514923/Cadmium_induces_matrix_metalloproteinase_9_expression_via_ROS_dependent_EGFR_NF_кB_and_AP_1_pathways_in_human_endothelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(15)30048-2 DB - PRIME DP - Unbound Medicine ER -