Abstract
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 Drosophila melanogaster 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 Drosophila 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.
Highlights
Toxic elements, such as the heavy metal, lead (Pb), have been affecting the daily lives of humans for more than three thousand years
The entry of Pb into the cardiovascular system has been suggested to occur via various calcium (Ca2+ ) channels [29,30], and Pb impairs the normal function of cardiac
We demonstrate practical applications of the optimized Förster resonance energy transfer (FRET)-based this study, we demonstrate practical applications of the optimized FRET-based genetically genetically encoded Pb biosensor Met-lead 1.44 M1 (Figure 1B) in two different systems: encoded Pb biosensor Met-lead 1.44 M1 (Figure 1B) in two different systems: in vitro in in vitro in induced pluripotent stem cell (iPSC)-derived cardiomyocytes (Figures 2 and 3) and in vivo in fruit flies (Figures iPSC-derived cardiomyocytes (Figures 2 and 3) and in vivo in fruit flies (Figures 4 and 5)
Summary
Toxic elements, such as the heavy metal, lead (Pb), have been affecting the daily lives of humans for more than three thousand years. A doctor of Chinese medicine in Taiwan illegally issued an incorrect prescription containing large amounts of Pb, which led to harmful effects for patients with ages ranging from 4 to 85 years old [9]. Pb can cause tissue damage that leads to neurological disorders, including cognitive deficits, low intelligence quotient (IQ), and attention-deficit hyperactivity disorder (ADHD) [10]. Pb can cause cardiovascular diseases (CVDs) such as secondary arterial hypertension [11], and circulatory illnesses including anemia [12]. These toxicological impacts of Pb can result from various pathways of Pb exposure, such as drinking contaminated water, breathing, eating, and physical contact with Pb
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
