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When an organism is invaded by drugs or chemical contaminants, it will stress-raise its transformation and experion capacity, so as to degrade or excrete the exogenous material as soon as possible, thus achieving self-protection, which is also known as the organism's external protective effect.
because this effect determines the duration of drug or pollutant stay in the body, thus affecting the drug efficacy or the toxicity of chemical pollutants, it has been extensively concerned by pharmacological and environmental toxicology research.
, the organism's external resistance is usually done by multiple protein systems.
, the role of THE ATP Binding Cassette Transporters is getting more and more attention.
the protein is a superfamily containing more than 200 kinds of proteins, expressed in a series of eukaryotic and pronuclear organisms, and widely distributed in tumors, liver, kidneys and blood-brain barrier and other organ tissues, is the tumor cell multidrug resistance, bacterial resistance, blood-brain barrier, placenta barrier drug resistance and aquatic animal pollutants toxicity resistance main reasons.
particularly, the main reason for the failure of chemotherapy treatment for cancer patients is the high expression of ABCBs (including Pgp and Bsep) in the ABC transport protein family, ABCCs (such as Mrps) and ABCGs (such as Bcrp), which give tumor cells high drug tolerance, hence the fact that these proteins are called multidrug-resistant proteins.
after a long period of research, scientists have a systematic understanding of the substrate recognition properties of ABC transport protein, but it is still unknown how the body can raise the expression level of transportprotein in the face of drug or environmental pollutant invasion, so as to achieve self-protection.
diagram: Quantum dot-induced zebrafish embryo ABC transport protein mechanism, in which, two quantum dots through the embryo protection membrane, on the one hand, by inducing the expression of pxR and other nuclear receptors, on the other hand, by inducing oxidative stress stress damage, stimulate the expression of the body's Nrf2 factor, two paths constitute the body's internal mechanism of self-protection, and through the increase of ABC transport protein function, to achieve the body's external defense.
, Dr. Yin Jian, Ph.D., of the Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, and others studied the mechanism of self-protection early in embryonic development, using zebrafish embryos as a model and cadmium carditin (CdTe) quantum dots as possible environmental toxins in different modified environments.
results show that abc transport protein in zebrafish embryos mediates the experion and detoxification of quantum dots, thus verifying the early conclusions of the laboratory.
at the same time, the researchers also found that nuclear receptors such as pregnane X receptor (Pregnane X receptor, PXR) and the nuclear factor NF-E2-related factor 2 (NF-E2-factor 2, Nrf2) can be in the embryo damage, stress increase transport protein, exogenous toxic substances to achieve embryo self-protection. More important
is that the above transcription factors precede the transport protein changes, and the range of change is more than 10 times that of transportprotein.
According to the team's early results and literature reports, found that the transport protein is broad in substrate, can be from heavy metals to polycyclic aromatic hydrocarbons, including a series of pollutants and cyanosis, polyphonic and other chemotherapy drugs to carry out stress response, and transcription factors as its internal regulatory factors, with early changes and higher sensitivity characteristics, so can be developed for environmental toxicity prevention and multi-drug drug-resistant tumor treatment.
first of all, the appearance of environmental pollution can be judged by the sensitive change of the translucent factor in aquatic animals.
secondly, through targeted transcription factors, it is possible to inhibit the emergence of multidrug resistance, to achieve the treatment of multidrug-resistant tumors.
the results are now published in the journal Environ Pollution in the field of environmental toxicology.
work has been supported by the National Key Research and Development Program, the National Natural Science Foundation project, the Jiangsu Province's forward-looking joint research project, and the National Postdoctoral Fund.
Source: Suzhou Institute of Biomedical Engineering and Technology.