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Alterations in manganese, copper, and zinc contents, and intracellular status of the metal-containing superoxide dismutase in human mesothelioma cells.
J Trace Elem Med Biol. 2008; 22(3):248-55.JT

Abstract

BACKGROUND AND AIM

Molecular diagnostics and therapeutics of human mesothelioma using disease-related markers present major challenges in clinical practice. To identify biochemical alternations that would be markers of human mesothelioma, we measured the intracellular steady-state levels of biologically important trace metals such as manganese (Mn), copper (Cu), and zinc (Zn) in a human mesothelial cell line, MeT-5A, and in five human mesothelioma cell lines (MSTO-211H, NCI-H226, NCI-H2052, NCI-H2452, ACC-MESO-1) by inductively coupled plasma-mass spectrometry (ICP-MS). We also aimed to investigate whether the alterations were related to the intracellular status of metal-containing superoxide dismutase (SOD).

RESULTS

There were no significant differences in the contents of the trace metals among MeT-5A, MSTO-211H, and ACC-MESO-1 cells. However, each of the other three mesothelioma cell lines had a unique characteristic in terms of the intracellular amounts of the metals; NCI-H226 contained an extremely high level of Mn, an amount 7.3-fold higher than that in MeT-5A. NCI-H2052 had significantly higher amounts of Cu (3.4-fold) and Zn (1.3-fold) compared with MeT-5A. NCI-H2452 contained about 5.8-fold the amount of Cu and 2.5-fold that of Mn compared with MeT-5A. As for the intracellular levels of copper/zinc-SOD (Cu/Zn-SOD) and manganese-SOD (Mn-SOD), those of Cu/Zn-SOD were relatively unchanged among the cells tested, and no notable correlation with Cu or Zn contents was observed. On the other hand, all mesothelioma cells highly expressed Mn-SOD compared with MeT-5A, and a very high expression of the enzyme with a robust activity was observed in the two mesothelioma cells (NCI-H226, NCI-H2452) containing a large amount of Mn.

CONCLUSIONS

In comparison with MeT-5A human mesothelial cells, some human mesothelioma cells had significantly higher amounts of Mn or Cu and one mesothelioma cell had a significantly higher amount of Zn. Interestingly, all mesothelioma cells overexpressed Mn-SOD compared with MeT-5A, and the cells whose Mn-SOD activity was increased contained higher amounts of Mn. It seemed that intracellular Mn content was positively correlated with Mn-SOD, suggesting that the intracellular Mn level is associated with Mn-SOD activity. These biochemical signatures could be potential disease-related markers of mesothelioma.

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Authors+Show Affiliations

Hasegawa S
Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. shase@nirs.go.jp
Koshikawa M
No affiliation info available
Takahashi I
No affiliation info available
Hachiya M
No affiliation info available
Furukawa T
No affiliation info available
Akashi M
No affiliation info available
Yoshida S
No affiliation info available
Saga T
No affiliation info available

MeSH

Cell LineCopperEpitheliumHumansIntracellular SpaceManganeseMass SpectrometryMesotheliomaSuperoxide DismutaseZinc

Pub Type(s)

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

Language

eng

PubMed ID

18755401

Citation

Hasegawa, Sumitaka, et al. "Alterations in Manganese, Copper, and Zinc Contents, and Intracellular Status of the Metal-containing Superoxide Dismutase in Human Mesothelioma Cells." Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS), vol. 22, no. 3, 2008, pp. 248-55.
Hasegawa S, Koshikawa M, Takahashi I, et al. Alterations in manganese, copper, and zinc contents, and intracellular status of the metal-containing superoxide dismutase in human mesothelioma cells. J Trace Elem Med Biol. 2008;22(3):248-55.
Hasegawa, S., Koshikawa, M., Takahashi, I., Hachiya, M., Furukawa, T., Akashi, M., Yoshida, S., & Saga, T. (2008). Alterations in manganese, copper, and zinc contents, and intracellular status of the metal-containing superoxide dismutase in human mesothelioma cells. Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS), 22(3), 248-55. https://doi.org/10.1016/j.jtemb.2008.05.001
Hasegawa S, et al. Alterations in Manganese, Copper, and Zinc Contents, and Intracellular Status of the Metal-containing Superoxide Dismutase in Human Mesothelioma Cells. J Trace Elem Med Biol. 2008;22(3):248-55. PubMed PMID: 18755401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alterations in manganese, copper, and zinc contents, and intracellular status of the metal-containing superoxide dismutase in human mesothelioma cells. AU - Hasegawa,Sumitaka, AU - Koshikawa,Michiko, AU - Takahashi,Isao, AU - Hachiya,Misao, AU - Furukawa,Takako, AU - Akashi,Makoto, AU - Yoshida,Satoshi, AU - Saga,Tsuneo, Y1 - 2008/07/18/ PY - 2008/01/23/received PY - 2008/04/23/revised PY - 2008/05/22/accepted PY - 2008/8/30/pubmed PY - 2009/2/24/medline PY - 2008/8/30/entrez SP - 248 EP - 55 JF - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) JO - J Trace Elem Med Biol VL - 22 IS - 3 N2 - BACKGROUND AND AIM: Molecular diagnostics and therapeutics of human mesothelioma using disease-related markers present major challenges in clinical practice. To identify biochemical alternations that would be markers of human mesothelioma, we measured the intracellular steady-state levels of biologically important trace metals such as manganese (Mn), copper (Cu), and zinc (Zn) in a human mesothelial cell line, MeT-5A, and in five human mesothelioma cell lines (MSTO-211H, NCI-H226, NCI-H2052, NCI-H2452, ACC-MESO-1) by inductively coupled plasma-mass spectrometry (ICP-MS). We also aimed to investigate whether the alterations were related to the intracellular status of metal-containing superoxide dismutase (SOD). RESULTS: There were no significant differences in the contents of the trace metals among MeT-5A, MSTO-211H, and ACC-MESO-1 cells. However, each of the other three mesothelioma cell lines had a unique characteristic in terms of the intracellular amounts of the metals; NCI-H226 contained an extremely high level of Mn, an amount 7.3-fold higher than that in MeT-5A. NCI-H2052 had significantly higher amounts of Cu (3.4-fold) and Zn (1.3-fold) compared with MeT-5A. NCI-H2452 contained about 5.8-fold the amount of Cu and 2.5-fold that of Mn compared with MeT-5A. As for the intracellular levels of copper/zinc-SOD (Cu/Zn-SOD) and manganese-SOD (Mn-SOD), those of Cu/Zn-SOD were relatively unchanged among the cells tested, and no notable correlation with Cu or Zn contents was observed. On the other hand, all mesothelioma cells highly expressed Mn-SOD compared with MeT-5A, and a very high expression of the enzyme with a robust activity was observed in the two mesothelioma cells (NCI-H226, NCI-H2452) containing a large amount of Mn. CONCLUSIONS: In comparison with MeT-5A human mesothelial cells, some human mesothelioma cells had significantly higher amounts of Mn or Cu and one mesothelioma cell had a significantly higher amount of Zn. Interestingly, all mesothelioma cells overexpressed Mn-SOD compared with MeT-5A, and the cells whose Mn-SOD activity was increased contained higher amounts of Mn. It seemed that intracellular Mn content was positively correlated with Mn-SOD, suggesting that the intracellular Mn level is associated with Mn-SOD activity. These biochemical signatures could be potential disease-related markers of mesothelioma. SN - 0946-672X UR - https://www.unboundmedicine.com/medline/citation/18755401/Alterations_in_manganese_copper_and_zinc_contents_and_intracellular_status_of_the_metal_containing_superoxide_dismutase_in_human_mesothelioma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0946-672X(08)00063-1 DB - PRIME DP - Unbound Medicine ER -