Metabolism Of Toxic Substances Research Articles

Molecular characterization and functional analysis of glutathione S-transferase genes of pine wood nematode (Bursaphelenchus xylophilus) for avermectin

Pine wilt disease (PWD), caused by Bursaphelenchus xylophilus (pine wood nematodes, PWNs), is a forest disease that seriously threatens the health of Pinus forestry. Glutathione S-transferases (GSTs) play important roles in xenobiotic metabolism, lipophilic compound transport, antioxidative stress reactions, anti-mutagenesis, and antitumor activity. The analysis and investigation of the specific functions of GSTs in the metabolism of toxic substances in nematodes are important for identifying potential target genes to control the spread and transmission of B. xylophilus. In this study, 51 Bx-GSTs were found in the genome of B. xylophilus. Two key Bx-gsts (Bx-gst12 and Bx-gst40) were analyzed when B. xylophilus was exposed to avermectin. The expression of Bx-gst12 and Bx-gst40 was significantly increased when B. xylophilus was exposed to 1.6 and 3.0 mg/mL avermectin solutions. Notably, combined silencing of both Bx-gst12 and Bx-gst40 did not further increase the mortality rates under avermectin exposure. Mortality rates were significantly increased in nematodes treated with dsRNA compared to control nematodes (p < 0.05) after RNAi. The feeding ability of nematodes was also significantly reduced after treatment with dsRNA. These results suggested that Bx-gsts are associated with the detoxification process and feeding behavior of B. xylophilus. Silencing Bx-gsts leads to increased susceptibility to nematicides and reduces the feeding ability of B. xylophilus. Therefore, Bx-gsts will be a new control target of PWNs in the future.

Identification of the AccCDK7 and AccCDK9 genes and their involvement in the response to resist external stress in Apis cerana cerana

Previous studies examining the functions of cyclin-dependent kinases (CDKs) have mainly focused on the regulation of the cell cycle. Recent studies have found that cyclin-dependent kinase 7 (CDK7) and cyclin-dependent kinase 9 (CDK9) play important roles in cell stress, metabolism of toxic substances and maintaining the stability of the internal environment. Here, we found that under stress conditions, the transcription and protein expression of AccCDK7 and AccCDK9 were induced to varying degrees. Meanwhile, the silencing of AccCDK7 and AccCDK9 also affected the expression of antioxidant genes and the activity of antioxidant enzymes, and reduced the survival rate of bees under high temperature stress. Furthermore, the exogenous overexpression of AccCDK7 and AccCDK9 improved the viability of yeast under stress conditions. Therefore, AccCDK7 and AccCDK9 may play roles in A.cerana cerana resistance to oxidative stress caused by external stimuli, potentially revealing a new mechanism of the honeybee response to oxidative stress.

Research progress of nuclear factor-erythroid 2 related factor 2 in acute lung injury

The anti-oxidant stress of the body is mainly mediated by the transcription factor nuclear factor-erythroid 2 related factor 2 (Nrf2). Nrf2 can promote cell protective gene expression. Nrf2 plays an important role in regulating the oxidative stress, the metabolism of toxic substances, the inflammation, the apoptosis, and the physiological functions of cells. Multiple studies have shown that the activation of Nrf2 alleviates oxidative stress and inflammation, plays an important role in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), and is expected to be potential targets for the prevention and treatment of ALI/ARDS. In this article we review the importance of Nrf2 and its activation pathway in preventing and treating ALI/ARDS for the aim of understanding its functional mechanism in ALI/ARDS, and providing a reliable reference for the pathogenesis and treatment of ALI/ARDS.

Challenges and opportunities in genome-wide environmental interaction (GWEI) studies

The interest in performing gene-environment interaction studies has seen a significant increase with the increase of advanced molecular genetics techniques. Practically, it became possible to investigate the role of environmental factors in disease risk and hence to investigate their role as genetic effect modifiers. The understanding that genetics is important in the uptake and metabolism of toxic substances is an example of how genetic profiles can modify important environmental risk factors to disease. Several rationales exist to set up gene-environment interaction studies and the technical challenges related to these studies-when the number of environmental or genetic risk factors is relatively small-has been described before. In the post-genomic era, it is now possible to study thousands of genes and their interaction with the environment. This brings along a whole range of new challenges and opportunities. Despite a continuing effort in developing efficient methods and optimal bioinformatics infrastructures to deal with the available wealth of data, the challenge remains how to best present and analyze genome-wide environmental interaction (GWEI) studies involving multiple genetic and environmental factors. Since GWEIs are performed at the intersection of statistical genetics, bioinformatics and epidemiology, usually similar problems need to be dealt with as for genome-wide association gene-gene interaction studies. However, additional complexities need to be considered which are typical for large-scale epidemiological studies, but are also related to "joining" two heterogeneous types of data in explaining complex disease trait variation or for prediction purposes.

Preventive medicine: biomonitoring and chemoprevention

The aim of chemoprevention is to delay or prevent the development of pathological conditions, or to correct abnormal regulatory mechanisms and in some cases even reverse the process. For this intervention to succeed, biomarkers must be found that characterize impaired health status in a phase when impairment is still reversible. Genotoxicological parameters may function as biomarkers of this kind, such as inhibition or delay of mitosis, inhibition of apoptosis, increase in the number of chromosomal aberrations, decrease in the capacity of DNA repairing enzymes, or parameters characterizing immunological status (eg. decreased NK activity). With the help of early signs, impending negative changes or illness (which could not be prevented without effective chemoprevention) can be predicted in apparently healthy individuals. Thus, the first and most important step in chemoprevention is risk characterization. Risk characterization is a complex concept, which includes risk analysis, risk assessment and risk management. Chemoprevention is a part of the latter process. Biomarkers, which can be studied mainly by up-to-date molecular biological methods, are used in discovering risk factors and also in the assessment of caused biological effects. Besides avoiding risk factors, it is very important to strengthen the protective mechanisms, to promote the metabolism of toxic substances, and to repair damage (ward off denaturation of macromolecules caused by free oxygen radicals with antioxidants for example). Chemopreventive agents are therefore diverse in their targets. Most of them have antioxidant properties, such as plant-derived substances, like glycosides, flavonoids, various vitamins, carotinoids, and some trace elements such as selenium. Another group of chemopreventive agents inhibit cell proliferation, or induce programmed cell death (apoptosis). Another group influence terminal differentiation, or inhibit angiogenesis. Some chemopreventive agents affect the metabolism or detoxification of xenobiotics, or boost the functions of the immune system. In many cases these effects are mediated by the rate of methylation of DNA molecules.

Protein engineering in studies on metabolism of toxic substances.

Expression of cytochrome P-450s, drug metabolizing enzymes, from their coding sequences in heterologous cells were developed and the enzymatically active P-450s were synthesized. cDNAs of various chimera or mutant P-450s were constructed and expressed. Thus, regions or residues important for the function of cytochrome P-450 were analyzed.

Metabolism of toxic substances in isolated hepatocytes

Chloroform and selenite toxicity have been studied in isolated hepatocytes. Two different toxic mechanisms, which lead to cellular lysis after distinct lag periods, are compared. Chloroform toxicity can be divided into 2 phases, a first phase characterized by chloroform metabolism and a second phase characterized by lipid peroxidation. GSH depletion during the first phase is claimed to be a prerequisite for lipid peroxidation in the second phase. Selenite metabolism leads to cofactor depletion as well. Selenite reduction via a GSH reductase dependent pathway exhausts the cells of NADPH and this effect can be related to cellular lysis.