scholarly journals Reciprocal regulation of glutathione S-transferase spliceforms and the Drosophila c-Jun N-terminal kinase pathway components

2004 ◽  
Vol 383 (3) ◽  
pp. 483-490 ◽  
Author(s):  
Rungrutai UDOMSINPRASERT ◽  
Marie A. BOGOYEVITCH ◽  
Albert J. KETTERMAN

In mammalian systems, detoxification enzymes of the GST (glutathione S-transferase) family regulate JNK (c-Jun N-terminal kinase) signal transduction by interaction with JNK itself or other proteins upstream in the JNK pathway. In the present study, we have studied GSTs and their interaction with components of the JNK pathway from Diptera. We have evaluated the effects of four Delta class Anopheles dirus GSTs, GSTD1-1, GSTD2-2, GSTD3-3 and GSTD4-4, on the activity of full-length recombinant Drosophila HEP (mitogen-activated protein kinase kinase 7; where HEP stands for hemipterous) and the Drosophila JNK, as well as the reciprocal effect of these kinases on GST activity. Interestingly, even though these four GSTs are alternatively spliced products of the same gene and share >60% identity, they exerted different effects on JNK activity. GSTD1-1 inhibited JNK activity, whereas the other three GST isoforms activated JNK. GSTD2-2, GSTD3-3 and GSTD4-4 were inhibited 50–80% by HEP or JNK but GSTD1-1 was not inhibited by JNK. However, there were some similarities in the actions of HEP and JNK on these GSTs. For example, binding constants for HEP or JNK inhibiting a GST were similar (20–70 nM). Furthermore, after incubation of the GSTs with JNK, both JNK and the GSTs changed catalytic properties. The substrate specificities of both GSTs and JNK were also altered after their co-incubation. In addition, glutathione modulated the effects of JNK on GST activity. These results emphasize that different GST spliceforms possess different properties, both in their catalytic function and in their regulation of signalling through the JNK pathway.

1998 ◽  
Vol 66 (3) ◽  
pp. 1142-1148 ◽  
Author(s):  
Jean-Marie Grzych ◽  
Jan De Bont ◽  
Jinli Liu ◽  
Jean-Loup Neyrinck ◽  
Josette Fontaine ◽  
...  

ABSTRACT Sera from calves vaccinated with the recombinant Schistosoma bovis-derived 28-kDa glutathione S-transferase (28GST) and subsequently naturally or experimentally exposed toSchistosoma mattheei were studied for their content of specific immunoglobulin G (IgG) and IgA antibodies to recombinantS. bovis 28GST as well as for their capacity to inhibit the enzymatic activity of the antigen. The results were analyzed in regard to the presence (natural infection) or absence (experimental infection) of a protective effect(s) (reductions in worm burden, egg load, fecal egg counts, and excretion of viable eggs) toward S. mattheei challenge. Under such conditions, no differences in the IgG- and IgA-specific antibodies to recombinant S. bovis28GST or in the ability to block the catalytic function of the antigen between the two groups were recorded. Nevertheless, correlation analysis between the specific antibody responses to recombinantS. bovis 28GST and the inhibition of GST activity suggested an association with IgG in experimentally infected vaccinated animals, while in naturally infected vaccinated calves, the inhibitory activity appeared to be linked to a greater degree with IgA. These results suggest that in contrast to schistosomiasis in humans, IgG antibodies in calves with schistosomiasis may exhibit inhibitory functions toward GST enzymatic activity or have a modulatory effect on IgA antibody properties. Furthermore, sera from animals immunized with recombinantS. bovis 28GST recognized the native S. mattheei 28GST and achieved comparable levels of inhibition of activity of recombinant S. bovis 28GST and S. matthei 28GST, indicating the presence of cross-reactive epitopes on these two molecules.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jobaida Akther ◽  
Akio Ebihara ◽  
Tsutomu Nakagawa ◽  
Laila N. Islam ◽  
Fumiaki Suzuki ◽  
...  

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/−), 31.4% had GSTT1 (−/+) alleles, and 6.4% had null genotypes (−/−) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/−, 30.5% were −/+, and 8.4% were −/−. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes.


Crustaceana ◽  
2017 ◽  
Vol 90 (13) ◽  
pp. 1563-1574 ◽  
Author(s):  
Onder Aksu ◽  
Nuran Cikcikoglu Yildirim ◽  
Durali Danabas ◽  
Numan Yildirim

In this study, we determined the effects of the textile dyes Remazol Brillant Blue R (RBBR) and Congo Red (CR) on the enzymatic activities of Glutathione S-Transferase (GST), cytochrome P450 (CYP1A1) and Lactate dehydrogenase (LDH), in hepatopancreas of Astacus leptodactylus. The crayfishes were exposed to 0.5, 1.0, and 2.0 mg/l of RBBR or CR, for 24 and 48 h. The recorded GST activity clearly increased after 24 or 48 h exposure to CR, compared to a control group (), but the changes of GST activity depending on time and dose were not statistically significant in the RRBR group (). The activity of CYP1A1 generally decreased, but LDH activity increased in the groups exposed to different doses of CR and RBBR, when compared to their control groups. Detoxification enzymes (as GST, and CYP1A1) and metabolic enzymes (as LDH) can be proven to make useful markers for further evaluating the physiological effects of CR and RBBR on crayfish.


2020 ◽  
Vol 17 (3) ◽  
pp. 191-199
Author(s):  
Seval Yilmaz ◽  
Fatih Mehmet Kandemir ◽  
Emre Kaya ◽  
Mustafa Ozkaraca

Objective: This study aimed to detect hepatic oxidative damage caused by aflatoxin B1 (AFB1), as well as to examine how propolis protects against hepatotoxic effects of AFB1. Method: Rats were split into four groups as control group, AFB1 group, propolis group, AFB1+ propolis group. Results: There was significant increase in malondialdehyde (MDA) level and tumor suppressor protein (TP53) gene expression, Glutathione (GSH) level, Catalase (CAT) activity, CAT gene expression decreased in AFB1 group in blood. MDA level and Glutathione-S-Transferase (GST) activity, GST and TP53 gene expressions increased in AFB1 group, whereas GSH level and CAT activity alongside CAT gene expression decreased in liver. AFB1+propolis group showed significant decrease in MDA level, GST activity, TP53 and GST gene expressions, GSH level and CAT activity and CAT gene expression increased in liver compared to AFB1 group. Conclusion: These results suggest that propolis may potentially be natural agent that prevents AFB1- induced oxidative stress and hepatotoxicity.


2007 ◽  
Vol 405 (3) ◽  
pp. 617-623 ◽  
Author(s):  
Emma V. Jones ◽  
Mark J. Dickman ◽  
Alan J. Whitmarsh

The JNK (c-Jun N-terminal kinase)/mitogen-activated protein kinase signalling pathway is a major mediator of stress responses in cells, including the response to DNA damage. DNA damage also causes the stabilization and activation of p73, a member of the p53 family of transcription factors. p73, like p53, can mediate apoptosis by up-regulating the expression of pro-apoptotic genes, including Bax (Bcl2-associated X protein) and PUMA (p53 up-regulated modulator of apoptosis). Changes in p73 expression have been linked to tumour progression, particularly in neuroblastomas, whereas in tumours that feature inactivated p53 there is evidence that p73 may mediate the apoptotic response to chemotherapeutic agents. In the present study, we demonstrate a novel link between the JNK signalling pathway and p73. We use pharmacological and genetic approaches to show that JNK is required for p73-mediated apoptosis induced by the DNA damaging agent cisplatin. JNK forms a complex with p73 and phosphorylates it at several serine and threonine residues. The mutation of JNK phosphorylation sites in p73 abrogates cisplatin-induced stabilization of p73 protein, leading to a reduction in p73 transcriptional activity and reduced p73-mediated apoptosis. Our results demonstrate that the JNK pathway is an important regulator of DNA damage-induced apoptosis mediated by p73.


2013 ◽  
Vol 22 (5) ◽  
pp. 523-531 ◽  
Author(s):  
K. Yamamoto ◽  
Y. Aso ◽  
N. Yamada

2013 ◽  
Vol 28 (4) ◽  
pp. 336-347 ◽  
Author(s):  
Daniela Vivenza ◽  
Mauro Feola ◽  
Ornella Garrone ◽  
Martino Monteverde ◽  
Marco Merlano ◽  
...  

Background Anthracyclines are among the most active drugs against breast cancer, but can exert cardiotoxic effects eventually resulting in congestive heart failure (CHF). Identifying breast cancer patients at high risk of developing cardiotoxicity after anthracycline therapy would be of value in guiding the use of these agents. Aims We determined whether polymorphisms in the renin-angiotensin-aldosterone system (RAAS) and in the glutathione S-transferase (GST) family of phase II detoxification enzymes might be useful predictors of left ventricular ejection fraction (LVEF) kinetics and risk of developing CHF. We sought correlations between the development of cardiotoxicity and gene polymorphisms in 48 patients with early breast cancer treated with adjuvant anthracycline chemotherapy. Methods We analyzed the following polymorphisms: p.Met235Thr and p.Thr174Met in angiotensinogen ( AGT), Ins/Del in angiotensin-converting enzyme ( ACE), A1166C in angiotensin II type-1 receptor ( AGTR1A), c.-344T>C in aldosterone synthase ( CYP11B2), p.Ile105Val in GSTP1. Additionally, we analyzed the presence or absence of the GSTT1 and GSTP1 genes. A LVEF <50% was detected at least once during the 3 years of follow-up period in 13 out of 48 patients (27.1%). Conclusion RAAS gene polymorphisms were not significantly associated with the development of cardiotoxicity. GSTM1 may be useful as a biomarker of higher risk of cardiotoxicity, as demonstrated in our cohort of patients (p=0.147).


Open Biology ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 180256 ◽  
Author(s):  
Noelia Pinal ◽  
Manuel Calleja ◽  
Ginés Morata

The Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family. It appears to be conserved in all animal species where it regulates important physiological functions involved in apoptosis, cell migration, cell proliferation and regeneration. In this review, we focus on the functions of JNK in Drosophila imaginal discs, where it has been reported that it can induce both cell death and cell proliferation. We discuss this apparent paradox in the light of recent findings and propose that the pro-apoptotic and the pro-proliferative functions are intrinsic properties of JNK activity. Whether one function or another is predominant depends on the cellular context.


2020 ◽  
Vol 34 (5) ◽  
pp. 647-651
Author(s):  
Edicarlos Castro ◽  
Carolina Pucci ◽  
Stefano Duarte ◽  
Nilda Roma Burgos ◽  
Te Ming Tseng

AbstractSafeners have been widely used to reduce phytotoxicity to crops, thus serving as an alternative weed control strategy. Benoxacor and fenclorim safeners have the potential to protect plants from herbicide phytotoxicity by increasing glutathione S-transferase (GST) activity within the plant. The study aimed to evaluate the safening effect of benoxacor and fenclorim on tomato against selected herbicides applied POST. The experiment was conducted in a greenhouse in a completely randomized designed with four replications in a 9 × 3 factorial scheme, where Factor A consisted of eight herbicides including a nontreated control, and Factor B consisted of two safeners including a nontreated control. The herbicide treatments were sulfentrazone (0.220 kg ai ha−1), fomesafen (0.280 kg ai ha−1), flumioxazin (0.070 kg ai ha−1), linuron (1.200 kg ai ha−1), metribuzin (0.840 kg ai ha−1), pyroxasulfone (0.220 kg ai ha−1), and bicyclopyrone (0.040 kg ai ha−1). Safener treatments consisted of benoxacor (0.67 g L−1) and fenclorim (10 µM). Tomato seeds were immersed in safener solution before sowing and herbicides were applied when tomato plants were at the 3-leaf stage, or 25 days after sowing. Visible injury was scored at 3, 7, 14, and 21 d after application (DAA), and shoot biomass was recorded 21 DAA. Seed treatment with fenclorim reduced injury caused by imazamox and bicyclopyrone by 5.5 and 1.3 times, respectively, whereas benoxacor reduced the injury from bicyclopyrone 1.3 times. In addition, tomato plants pretreated with fenclorim showed a lesser reduction in biomass after application of imazamox, fomesafen, and metribuzin, whereas plants pretreated with benoxacor showed lesser biomass reduction after metribuzin application. Thus, the use of safeners promotes greater crop selectivity, allowing the application of herbicides with different mechanisms of action on the crop.


2020 ◽  
Vol 25 (7) ◽  
pp. 1329-1342
Author(s):  
Jia Chen ◽  
Xianyan Ye ◽  
Jing Wang ◽  
Bin Xia ◽  
Tianrong Xin

Diflubenzuron, a benzoylphenylurea insecticide that interferes with chitin biosynthesis, causes arthropods to moult abnormally and die. However, its mechanism of action in Tetranychus cinnabarinus is still unclear. In order to explore the effects of different sublethal concentrations of diflubenzuron on T. cinnabarinus, we conducted a high-throughput RNA-seq technology to identify the variations in transcriptomic profile of T. cinnabarinus larvae. The results revealed that 470 and 49 differentially expressed genes were identified in LC50-and LC70-treated groups, comparing with the control. We also identified and analyzed the detoxification enzymes involved in the transcritome of T. cinnabarinus, including 34 cytochrome P450 genes, 17 glutathione-s-transferase genes (GSTs), 12 acetylcholinesterase genes (AChEs) and 9 ABC transporter genes. In addition, differentially expressed genes analysis showed that the gene expression levels of detoxification enzymes were generally enhanced. At the same time, seven and eleven genes were involved in chitin synthesis and degradation ways, respectively. The expression level of most genes involved in chitin synthesis and degradation pathway were generally up-regulated after exposure to sublethal concentrations of diflubenzuron. Moreover, for transcriptome validation, the mRNA expression results of ten specially expressed genes by quantitative real-time PCR demonstrated that these gene expression trends were consistent with that of the transcriptome data. Together, all these results suggested that sublethal concentrations of diflubenzuron exposure affected gene expression of major detoxification enzymes and chitin metabolism genes in T. cinnabarinus larvae. These findings may be helpful to further understand the possible molecular mechanism of benzoylphenylurea insecticides in T. cinnabarinus, as well as in other spider mites.


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