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Anchoring-Detection Fluorescent Probe for Investigating Microcystin-LR-Induced Plasma Membrane Damage
Zhaomin Wang1, Tianhe Fang2,3, Syed Turab Raza1,4
1State Key Laboratory for Vegetation Structure, Functions and Construction, Microcystins Pollution Control Engineering Research Center of Yunnan Education Department, Yunnan Key Laboratory of Ecological Protection and Resource Utilization of River-lake Networks, Yunnan University, Kunming 650500, China.
Abstract:
Microcystin-LR (MC-LR), derived from cyanobacterial blooms, is a highly potent hepatotoxin that can enter the human body through ingestion, inhalation, and dermal absorption. Deciphering the toxic mechanism of MC-LR can provide insights into pathogenesis, which is valuable for ensuring drinking water safety and health. However, due to the lack of suitable in situ visualization tools, researchers have been unable to determine the plasma membrane damage process caused by MC-LR, including the tension, morphology, and permeability changes. With this research, we propose a rational strategy to develop a robust anchoring and specific recognition fluorescent probe, which can facilitate simultaneous fluorescence imaging of the plasma membrane and MC-LR. Using the probe, we observed the accumulation of MC-LR on the plasma membrane. More interestingly, fluorescence imaging using the unique anchoring-detection probe technique reveals a damage process of the plasma membrane of primary hepatocytes caused by MC-LR: during the damage process, the plasma membrane sequentially undergoes contraction, wrinkling, and ulceration, ultimately leading to the loss of membrane permeability regulation function, and the process is accompanied by severe nuclear collapse and nuclear envelope contraction.
Insights
Researchers developed a novel fluorescent probe to visualize how microcystin-LR (MC-LR) damages liver cells. The probe revealed MC-LR causes plasma membrane contraction, wrinkling, and permeability loss, impacting cell integrity and nuclear structure.
Area of Science:
- Toxicology
- Cell Biology
- Biochemistry
Background:
- Microcystin-LR (MC-LR) is a potent cyanobacterial hepatotoxin with significant public health implications.
- Understanding MC-LR's toxic mechanism is crucial for drinking water safety and disease pathogenesis.
- Existing visualization tools are insufficient to study MC-LR-induced plasma membrane damage in situ.
Purpose of the Study:
- To develop a fluorescent probe for simultaneous imaging of plasma membranes and MC-LR.
- To elucidate the dynamic process of plasma membrane damage induced by MC-LR.
- To investigate the effects of MC-LR on hepatocyte structure and function.
Main Methods:
- Development of a robust anchoring and specific recognition fluorescent probe.
- Simultaneous fluorescence imaging of plasma membrane and MC-LR accumulation.
- In situ observation of primary hepatocyte damage using the developed probe.
Main Results:
- The probe successfully visualized MC-LR accumulation on the plasma membrane.
- MC-LR induced sequential plasma membrane changes: contraction, wrinkling, and ulceration.
- Hepatocyte damage involved loss of membrane permeability regulation, nuclear collapse, and nuclear envelope contraction.
Conclusions:
- The developed fluorescent probe enables real-time visualization of MC-LR-induced cellular damage.
- MC-LR causes distinct stages of plasma membrane damage, leading to cell dysfunction.
- This study provides critical insights into MC-LR hepatotoxicity and potential health risks.
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