Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning
The heavy metal, lead (Pb) can irreversibly damage the human nervous system. To help understand Pb-induced damage, we applied a genetically encoded Förster resonance energy transfer (FRET)-based Pb biosensor Met-lead 1.44 M1 to two living systems to monitor the concentration of Pb: induced pluripote...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Biosensors |
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| Online Access: | https://www.mdpi.com/2079-6374/11/10/371 |
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| author | De-Ming Yang Yu-Fen Chang |
| author_facet | De-Ming Yang Yu-Fen Chang |
| author_sort | De-Ming Yang |
| collection | DOAJ |
| description | The heavy metal, lead (Pb) can irreversibly damage the human nervous system. To help understand Pb-induced damage, we applied a genetically encoded Förster resonance energy transfer (FRET)-based Pb biosensor Met-lead 1.44 M1 to two living systems to monitor the concentration of Pb: induced pluripotent stem cell (iPSC)-derived cardiomyocytes as a semi-tissue platform and <i>Drosophila melanogaster</i> fruit flies as an in vivo animal model. Different FRET imaging modalities were used to obtain FRET signals, which represented the presence of Pb in the tested samples in different spatial dimensions. Using iPSC-derived cardiomyocytes, the relationship between beating activity (20–24 beats per minute, bpm) determined from the fluctuation of fluorescent signals and the concentrations of Pb represented by the FRET emission ratio values of Met-lead 1.44 M1 was revealed from simultaneous measurements. Pb (50 μM) affected the beating activity of cardiomyocytes, whereas two drugs that stop the entry of Pb differentially affected this beating activity: verapamil (2 μM) did not reverse the cessation of beating, whereas 2-APB (50 μM) partially restored this activity (16 bpm). The results clearly demonstrate the potential of this biosensor system as an anti-Pb drug screening application. In the <i>Drosophila</i> model, Pb was detected within the adult brain or larval central nervous system (Cha-gal4 > UAS-Met-lead 1.44 M1) using fast epifluorescence and high-resolution two-photon 3D FRET ratio image systems. The tissue-specific expression of Pb biosensors provides an excellent opportunity to explore the possible Pb-specific populations within living organisms. We believe that this integrated Pb biosensor system can be applied to the prevention of Pb poisoning and advanced research on Pb neurotoxicology. |
| first_indexed | 2024-03-10T06:41:18Z |
| format | Article |
| id | doaj.art-4817789a19f04e5d96783a134d85b4a5 |
| institution | Directory Open Access Journal |
| issn | 2079-6374 |
| language | English |
| last_indexed | 2024-03-10T06:41:18Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biosensors |
| spelling | doaj.art-4817789a19f04e5d96783a134d85b4a52023-11-22T17:35:42ZengMDPI AGBiosensors2079-63742021-10-01111037110.3390/bios11100371Versatile Cell and Animal Models for Advanced Investigation of Lead PoisoningDe-Ming Yang0Yu-Fen Chang1Microscopy Service Laboratory, Basic Research Division, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, TaiwanNational Biotechnology Research Park, LumiSTAR Biotechnology Inc., Taipei City 115, TaiwanThe heavy metal, lead (Pb) can irreversibly damage the human nervous system. To help understand Pb-induced damage, we applied a genetically encoded Förster resonance energy transfer (FRET)-based Pb biosensor Met-lead 1.44 M1 to two living systems to monitor the concentration of Pb: induced pluripotent stem cell (iPSC)-derived cardiomyocytes as a semi-tissue platform and <i>Drosophila melanogaster</i> fruit flies as an in vivo animal model. Different FRET imaging modalities were used to obtain FRET signals, which represented the presence of Pb in the tested samples in different spatial dimensions. Using iPSC-derived cardiomyocytes, the relationship between beating activity (20–24 beats per minute, bpm) determined from the fluctuation of fluorescent signals and the concentrations of Pb represented by the FRET emission ratio values of Met-lead 1.44 M1 was revealed from simultaneous measurements. Pb (50 μM) affected the beating activity of cardiomyocytes, whereas two drugs that stop the entry of Pb differentially affected this beating activity: verapamil (2 μM) did not reverse the cessation of beating, whereas 2-APB (50 μM) partially restored this activity (16 bpm). The results clearly demonstrate the potential of this biosensor system as an anti-Pb drug screening application. In the <i>Drosophila</i> model, Pb was detected within the adult brain or larval central nervous system (Cha-gal4 > UAS-Met-lead 1.44 M1) using fast epifluorescence and high-resolution two-photon 3D FRET ratio image systems. The tissue-specific expression of Pb biosensors provides an excellent opportunity to explore the possible Pb-specific populations within living organisms. We believe that this integrated Pb biosensor system can be applied to the prevention of Pb poisoning and advanced research on Pb neurotoxicology.https://www.mdpi.com/2079-6374/11/10/371<i>Drosophila melanogaster</i>fluorescence resonance energy transferMet-lead 1.44 M1Pb biosensor |
| spellingShingle | De-Ming Yang Yu-Fen Chang Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning Biosensors <i>Drosophila melanogaster</i> fluorescence resonance energy transfer Met-lead 1.44 M1 Pb biosensor |
| title | Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning |
| title_full | Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning |
| title_fullStr | Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning |
| title_full_unstemmed | Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning |
| title_short | Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning |
| title_sort | versatile cell and animal models for advanced investigation of lead poisoning |
| topic | <i>Drosophila melanogaster</i> fluorescence resonance energy transfer Met-lead 1.44 M1 Pb biosensor |
| url | https://www.mdpi.com/2079-6374/11/10/371 |
| work_keys_str_mv | AT demingyang versatilecellandanimalmodelsforadvancedinvestigationofleadpoisoning AT yufenchang versatilecellandanimalmodelsforadvancedinvestigationofleadpoisoning |