Effects of cadmium on structure and enzymatic activity of Cu,Zn-SOD and oxidative status in neural cells

Yen-Hua Huang, Chwen-Ming Shih, Chang Jen Huang, Chun-Mao Lin, Chih-Ming Chou, Meng Ling Tsai, Tsang Pai Liu, Jen Fu Chiu, Chien-Tsu Chen

研究成果: 雜誌貢獻文章

69 引文 (Scopus)

摘要

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder disease. Ten percent of the ALS patients are congenital (familial ALS), and the other 90% are sporadic ALS (SALS). It has been shown that mutations found in the Cu,Zn-SOD cause 20% of the familial ALS due to its low enzyme activity. We hypothesized that heavy metals may interfere the structure of Cu,Zn-SOD protein to suppress its activity in some of the SALS. In this study, we expressed and characterized the recombinant human Cu,Zn-SOD under various concentrations of Cu 2+, Zn 2+, and Cd 2+. By atomic absorption spectrophotometry, we demonstrated that adding of cadmium significantly increased the content of cadmium ion, but reduced its Zn 2+ content and enzyme activity of the Cu,Zn-SOD protein. The data of circular dichroism spectra demonstrated that the secondary structure of Cu,Zn-SOD/Cd is different from Cu,Zn-SOD, but close to apo-SOD. In addition to the effect of cadmium on Cu,Zn-SOD, cadmium was also shown to induce neural cell apoptosis. To further investigate the mechanism of neural cell apoptosis induced by cadmium, we used proteomics to analyze the altered protein expressions in neural cells treated with cadmium. The altered proteins include cellular structural proteins, stress-related and chaperone proteins, proteins involved in reactive oxygen species (ROS), enzyme proteins, and proteins that mediated cell death and survival signaling. Taken together, in this paper, we demonstrate that cadmium decreases the content of Zn 2+, changes the conformation of Cu,Zn-SOD protein to decrease its enzyme activity, and causes oxidative stress-induced neural cell apoptosis.
原文英語
頁(從 - 到)577-589
頁數13
期刊Journal of Cellular Biochemistry
98
發行號3
DOIs
出版狀態已發佈 - 六月 1 2006

指紋

Cadmium
Proteins
Enzyme activity
Amyotrophic Lateral Sclerosis
Enzymes
Apoptosis
Neurodegenerative Diseases
Atomic Spectrophotometry
Oxidative stress
Spectrophotometry
Cell death
Circular Dichroism
Heat-Shock Proteins
Heavy Metals
Proteomics
Conformations
Reactive Oxygen Species
Cell Survival
Oxidative Stress
Cell Death

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

引用此文

Effects of cadmium on structure and enzymatic activity of Cu,Zn-SOD and oxidative status in neural cells. / Huang, Yen-Hua; Shih, Chwen-Ming; Huang, Chang Jen; Lin, Chun-Mao; Chou, Chih-Ming; Tsai, Meng Ling; Liu, Tsang Pai; Chiu, Jen Fu; Chen, Chien-Tsu.

於: Journal of Cellular Biochemistry, 卷 98, 編號 3, 01.06.2006, p. 577-589.

研究成果: 雜誌貢獻文章

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title = "Effects of cadmium on structure and enzymatic activity of Cu,Zn-SOD and oxidative status in neural cells",
abstract = "Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder disease. Ten percent of the ALS patients are congenital (familial ALS), and the other 90{\%} are sporadic ALS (SALS). It has been shown that mutations found in the Cu,Zn-SOD cause 20{\%} of the familial ALS due to its low enzyme activity. We hypothesized that heavy metals may interfere the structure of Cu,Zn-SOD protein to suppress its activity in some of the SALS. In this study, we expressed and characterized the recombinant human Cu,Zn-SOD under various concentrations of Cu 2+, Zn 2+, and Cd 2+. By atomic absorption spectrophotometry, we demonstrated that adding of cadmium significantly increased the content of cadmium ion, but reduced its Zn 2+ content and enzyme activity of the Cu,Zn-SOD protein. The data of circular dichroism spectra demonstrated that the secondary structure of Cu,Zn-SOD/Cd is different from Cu,Zn-SOD, but close to apo-SOD. In addition to the effect of cadmium on Cu,Zn-SOD, cadmium was also shown to induce neural cell apoptosis. To further investigate the mechanism of neural cell apoptosis induced by cadmium, we used proteomics to analyze the altered protein expressions in neural cells treated with cadmium. The altered proteins include cellular structural proteins, stress-related and chaperone proteins, proteins involved in reactive oxygen species (ROS), enzyme proteins, and proteins that mediated cell death and survival signaling. Taken together, in this paper, we demonstrate that cadmium decreases the content of Zn 2+, changes the conformation of Cu,Zn-SOD protein to decrease its enzyme activity, and causes oxidative stress-induced neural cell apoptosis.",
keywords = "Altered protein profile, Amylotrophic lateral sclerosis (ALS), Cadmium, Cu,Zn-SOD, Oxidative stress, Proteomics",
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T1 - Effects of cadmium on structure and enzymatic activity of Cu,Zn-SOD and oxidative status in neural cells

AU - Huang, Yen-Hua

AU - Shih, Chwen-Ming

AU - Huang, Chang Jen

AU - Lin, Chun-Mao

AU - Chou, Chih-Ming

AU - Tsai, Meng Ling

AU - Liu, Tsang Pai

AU - Chiu, Jen Fu

AU - Chen, Chien-Tsu

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder disease. Ten percent of the ALS patients are congenital (familial ALS), and the other 90% are sporadic ALS (SALS). It has been shown that mutations found in the Cu,Zn-SOD cause 20% of the familial ALS due to its low enzyme activity. We hypothesized that heavy metals may interfere the structure of Cu,Zn-SOD protein to suppress its activity in some of the SALS. In this study, we expressed and characterized the recombinant human Cu,Zn-SOD under various concentrations of Cu 2+, Zn 2+, and Cd 2+. By atomic absorption spectrophotometry, we demonstrated that adding of cadmium significantly increased the content of cadmium ion, but reduced its Zn 2+ content and enzyme activity of the Cu,Zn-SOD protein. The data of circular dichroism spectra demonstrated that the secondary structure of Cu,Zn-SOD/Cd is different from Cu,Zn-SOD, but close to apo-SOD. In addition to the effect of cadmium on Cu,Zn-SOD, cadmium was also shown to induce neural cell apoptosis. To further investigate the mechanism of neural cell apoptosis induced by cadmium, we used proteomics to analyze the altered protein expressions in neural cells treated with cadmium. The altered proteins include cellular structural proteins, stress-related and chaperone proteins, proteins involved in reactive oxygen species (ROS), enzyme proteins, and proteins that mediated cell death and survival signaling. Taken together, in this paper, we demonstrate that cadmium decreases the content of Zn 2+, changes the conformation of Cu,Zn-SOD protein to decrease its enzyme activity, and causes oxidative stress-induced neural cell apoptosis.

AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder disease. Ten percent of the ALS patients are congenital (familial ALS), and the other 90% are sporadic ALS (SALS). It has been shown that mutations found in the Cu,Zn-SOD cause 20% of the familial ALS due to its low enzyme activity. We hypothesized that heavy metals may interfere the structure of Cu,Zn-SOD protein to suppress its activity in some of the SALS. In this study, we expressed and characterized the recombinant human Cu,Zn-SOD under various concentrations of Cu 2+, Zn 2+, and Cd 2+. By atomic absorption spectrophotometry, we demonstrated that adding of cadmium significantly increased the content of cadmium ion, but reduced its Zn 2+ content and enzyme activity of the Cu,Zn-SOD protein. The data of circular dichroism spectra demonstrated that the secondary structure of Cu,Zn-SOD/Cd is different from Cu,Zn-SOD, but close to apo-SOD. In addition to the effect of cadmium on Cu,Zn-SOD, cadmium was also shown to induce neural cell apoptosis. To further investigate the mechanism of neural cell apoptosis induced by cadmium, we used proteomics to analyze the altered protein expressions in neural cells treated with cadmium. The altered proteins include cellular structural proteins, stress-related and chaperone proteins, proteins involved in reactive oxygen species (ROS), enzyme proteins, and proteins that mediated cell death and survival signaling. Taken together, in this paper, we demonstrate that cadmium decreases the content of Zn 2+, changes the conformation of Cu,Zn-SOD protein to decrease its enzyme activity, and causes oxidative stress-induced neural cell apoptosis.

KW - Altered protein profile

KW - Amylotrophic lateral sclerosis (ALS)

KW - Cadmium

KW - Cu,Zn-SOD

KW - Oxidative stress

KW - Proteomics

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