Expression of metallothionein isoform 3 (MT-3) determines the choice between apoptotic or necrotic cell death in Cd+2-exposed human proximal tubule cells
This laboratory has shown that the third isoform of metallothionein (MT-3) is expressed in the human kidney in situ, including the cells of the proximal tubule. A subsequent analysis of MT-3 expression in cell cultures derived from the human proximal tubule (HPT) demonstrated that mortal HPT cells e...
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| Veröffentlicht in: | Toxicological sciences Jg. 80; H. 2; S. 358 |
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| Abstract | This laboratory has shown that the third isoform of metallothionein (MT-3) is expressed in the human kidney in situ, including the cells of the proximal tubule. A subsequent analysis of MT-3 expression in cell cultures derived from the human proximal tubule (HPT) demonstrated that mortal HPT cells expressed MT-3, while the HPV-immortalized HK-2 cells had no expression of MT-3. In the present study, the effect of MT-3 expression on Cd(+2)-induced cytotoxicity was determined by stable transfection of the MT-3 coding sequence into the HK-2 cell line. The results demonstrated that HK-2 cells stably transfected with MT-3 were more sensitive to the cytotoxic effects of Cd(+2). Furthermore, this increase in Cd(+2)-induced cytotoxicity was correlated to an alteration in the mechanism of cell death, being changed from an apoptotic mechanism in cells not expressing the MT-3 gene to a necrotic mechanism in cells expressing the MT-3 gene. The present study provides evidence that MT-3 could play a role in controlling the choice between apoptosis and necrosis in multiple epithelial cell types of the human kidney. |
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| AbstractList | This laboratory has shown that the third isoform of metallothionein (MT-3) is expressed in the human kidney in situ, including the cells of the proximal tubule. A subsequent analysis of MT-3 expression in cell cultures derived from the human proximal tubule (HPT) demonstrated that mortal HPT cells expressed MT-3, while the HPV-immortalized HK-2 cells had no expression of MT-3. In the present study, the effect of MT-3 expression on Cd(+2)-induced cytotoxicity was determined by stable transfection of the MT-3 coding sequence into the HK-2 cell line. The results demonstrated that HK-2 cells stably transfected with MT-3 were more sensitive to the cytotoxic effects of Cd(+2). Furthermore, this increase in Cd(+2)-induced cytotoxicity was correlated to an alteration in the mechanism of cell death, being changed from an apoptotic mechanism in cells not expressing the MT-3 gene to a necrotic mechanism in cells expressing the MT-3 gene. The present study provides evidence that MT-3 could play a role in controlling the choice between apoptosis and necrosis in multiple epithelial cell types of the human kidney. This laboratory has shown that the third isoform of metallothionein (MT-3) is expressed in the human kidney in situ, including the cells of the proximal tubule. A subsequent analysis of MT-3 expression in cell cultures derived from the human proximal tubule (HPT) demonstrated that mortal HPT cells expressed MT-3, while the HPV-immortalized HK-2 cells had no expression of MT-3. In the present study, the effect of MT-3 expression on Cd(+2)-induced cytotoxicity was determined by stable transfection of the MT-3 coding sequence into the HK-2 cell line. The results demonstrated that HK-2 cells stably transfected with MT-3 were more sensitive to the cytotoxic effects of Cd(+2). Furthermore, this increase in Cd(+2)-induced cytotoxicity was correlated to an alteration in the mechanism of cell death, being changed from an apoptotic mechanism in cells not expressing the MT-3 gene to a necrotic mechanism in cells expressing the MT-3 gene. The present study provides evidence that MT-3 could play a role in controlling the choice between apoptosis and necrosis in multiple epithelial cell types of the human kidney.This laboratory has shown that the third isoform of metallothionein (MT-3) is expressed in the human kidney in situ, including the cells of the proximal tubule. A subsequent analysis of MT-3 expression in cell cultures derived from the human proximal tubule (HPT) demonstrated that mortal HPT cells expressed MT-3, while the HPV-immortalized HK-2 cells had no expression of MT-3. In the present study, the effect of MT-3 expression on Cd(+2)-induced cytotoxicity was determined by stable transfection of the MT-3 coding sequence into the HK-2 cell line. The results demonstrated that HK-2 cells stably transfected with MT-3 were more sensitive to the cytotoxic effects of Cd(+2). Furthermore, this increase in Cd(+2)-induced cytotoxicity was correlated to an alteration in the mechanism of cell death, being changed from an apoptotic mechanism in cells not expressing the MT-3 gene to a necrotic mechanism in cells expressing the MT-3 gene. The present study provides evidence that MT-3 could play a role in controlling the choice between apoptosis and necrosis in multiple epithelial cell types of the human kidney. |
| Author | Sens, Donald A Garrett, Scott H Somji, Seema Gurel, Volkan Sens, Mary Ann |
| Author_xml | – sequence: 1 givenname: Seema surname: Somji fullname: Somji, Seema organization: Department of Pathology, School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, North Dakota 58202-9037, USA – sequence: 2 givenname: Scott H surname: Garrett fullname: Garrett, Scott H – sequence: 3 givenname: Mary Ann surname: Sens fullname: Sens, Mary Ann – sequence: 4 givenname: Volkan surname: Gurel fullname: Gurel, Volkan – sequence: 5 givenname: Donald A surname: Sens fullname: Sens, Donald A |
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| SubjectTerms | Apoptosis - drug effects Cadmium - toxicity Caspase 3 Caspases - metabolism Cell Death - drug effects Cell Line Cell Survival - drug effects DNA - genetics Fluorescent Dyes Humans Indoles Isomerism Kidney Tubules, Proximal - drug effects Kidney Tubules, Proximal - pathology L-Lactate Dehydrogenase - metabolism Necrosis Nerve Tissue Proteins - biosynthesis Nerve Tissue Proteins - genetics Reverse Transcriptase Polymerase Chain Reaction Transfection |
| Title | Expression of metallothionein isoform 3 (MT-3) determines the choice between apoptotic or necrotic cell death in Cd+2-exposed human proximal tubule cells |
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