NDLI: Subcellular localization of a fluorescent derivative of Cu<sup>II</sup>(atsm) offers insight into the neuroprotective action of Cu<sup>II</sup>(atsm)

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Combination of PAGE and LA-ICP-MS as an analytical workflow in metallomics: state of the art, new quantification strategies, advantages and limitations

Subcellular localization of a fluorescent derivative of Cu^II(atsm) offers insight into the neuroprotective action of Cu^II(atsm)

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Metallomics Vol - 3 Issue - 9

Metallomics Vol - 3 Issue - 8

Metallomics Vol - 3 Issue - 7

Metallomics Vol - 3 Issue - 6

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Metallomics Vol - 3 Issue - 3

Metallomics Vol - 3 Issue - 2

Metallomics Vol -2

Metallomics Vol -1

Subcellular localization of a fluorescent derivative of Cu^II(atsm) offers insight into the neuroprotective action of Cu^II(atsm)

Content Provider	Royal Society of Chemistry (RSC)
Author	Crouch, Peter J. White, Anthony R. Paterson, Brett M. Liddell, Jeffrey R. Lim, SinChun Price, Katherine Ann Donnelly, Paul S.
Copyright Year	2011
Abstract	Copper complexes of bis(thiosemicarbazone) (CuII(btsc)s) have been studied as potential anti-cancer agents and hypoxia imaging agents. More recently, CuII(btsc)s have been identified as possessing potent neuroprotective properties in cell and animal models of neurodegenerative disease. Despite their broad range of pharmacological activity little is known about how cells traffic CuII(btsc)s and how this relates to potential anti-cancer or neuroprotective outcomes. One method of investigating sub-cellular localization of metal complexes is through confocal fluorescence imaging of the compounds in cells. Previously we harnessed the fluorescence of a pyrene group attached to diacetyl-bis(N4-methylthiosemicarbazonato)copper(II)) (CuII(atsm)), (CuIIL1). We demonstrated that CuIIL1 was partially localized to lysosomes in HeLa cancer epithelial cells. Here we extend these studies to map the sub-cellular localization of CuIIL1 in M17 neuroblastoma cells. Treatment of M17 or HeLa cells led to rapid association of the Cu-complex into distinct punctate structures that partially co-localized with lysosomes as assessed by co-localization with Lysotracker and acridine orange. No localization to early or late endosomes, the nucleus or mitochondria was observed. We also found evidence for a limited association of CuIIL1 with autophagic structures, however, this did not account for the majority of the punctate localization of CuIIL1. In addition, CuIIL1 revealed partial localization with ER Tracker and was found to inhibit ER stress induced by tunicamycin. This is the first report to comprehensively characterize the sub-cellular localization of a CuII(atsm) derivative in cells of a neuronal origin and the partial association with lysosome/autophagic structures and the ER may have a potential role in neuroprotection.
Starting Page	1280
Ending Page	1290
Page Count	11
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	3
Issue Number	12
Journal	Metallomics
DOI	10.1039/c1mt00092f
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Neuroprotection Tunicamycin Lysosome Tumor hypoxia Fluorescence microscope Neuroblastoma HeLa Acridine orange Mitochondrion Pyrene Lysotracker Neurodegeneration Group N Semicarbazone Copper Endoplasmic reticulum Cancer
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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Subcellular localization of a fluorescent derivative of Cu^II(atsm) offers insight into the neuroprotective action of Cu^II(atsm)

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Subcellular localization of a fluorescent derivative of CuII(atsm) offers insight into the neuroprotective action of CuII(atsm)

Subcellular localization of a fluorescent derivative of Cu^II(atsm) offers insight into the neuroprotective action of Cu^II(atsm)