Characterization and Mutational Analysis of Omega-Class GST (GSTO1) from Apis cerana cerana, a Gene Involved in Response to Oxidative Stress

Meng, Fei; Zhang, Yuanying; Liu, Feng; Guo, Xingqi; Xu, Baohua

doi:10.1371/journal.pone.0093100

Cited by 41 publications

(40 citation statements)

References 52 publications

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“…In cancer tissue, inflammation has been triggered and angiogenesis is extensive, therefore further reactive oxygen species are produced. A recent study identified that GSTO1 provides protection from oxidative stress (20). This result is consistent with the results of the present study that DISS cells that expressed increased levels of GSTO1 responded well to PDT.…”

Section: Signal -------------------------------------------------------supporting

confidence: 94%

Differences in the sensitivity of ovarian cancer to photodynamic therapy and the mechanisms for those differences

et al. 2017

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Abstract. Protoporphyrin IX (PpIX) levels are crucial to the antitumor action of photodynamic therapy (PDT). In the present study, the underling molecular mechanisms for the variation in PpIX levels in ovarian cancer cells were investigated. Five ovarian cancer cell lines were subcutaneously grafted onto the backs of nude mice. Once tumors had developed, 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA) was administered intraperitoneally and the tumor was irradiated twice/week. PpIX levels in the tumor were assayed using high-performance liquid chromatography. Enzymes involved in heme synthesis and degradation were screened using a microarray technique. Expression of the glutathione transferase Omega-1 (GSTO1) gene involved in the conversion of PpIX into heme in cells was quantified using the reverse transcription-quantitative polymerase chain reaction. In HTOA, HRA and DISS cells, PDT resulted in significant tumor shrinkage in comparison with the controls. In MCAS and TOV21G cells, no significant alterations in tumor growth were identified compared with the untreated cells. PpIX levels increased significantly in HTOA, DISS and HRA cells compared with in MCAS and TOV21G cells. A comparison of genetic profiles using PDT-sensitive DISS cells and PDT-resistant MCAS cells indicated that MCAS cells exhibited significantly increased levels of δ-aminolevulinate synthase (a rate-limiting enzyme in heme synthesis), heme oxygenase 2 (an enzyme that degrades heme into biliverdin), and biliverdin reductase B (an enzyme that reduces biliverdin into bilirubin) in comparison with DISS cells. The level of GSTO1 expression in HTOA, HRA and DISS cells was ~2.5-fold that in MCAS and TOV21G cells. Sensitivity to PDT is related to PpIX levels in cells. The results of the present study suggested that PpIX tends not to accumulate in PDT-resistant cells despite active heme synthesis and degradation, and that high levels of GSTO1 expression are associated with increased sensitivity to PDT. IntroductionThe standard treatment for ovarian cancer is surgery followed by anticancer therapy (1). A total of ~70% of advanced ovarian cancer recurs, so advanced ovarian cancer ultimately has a 5-year survival rate of between 30 and 40% (2). Ovarian cancer has the highest mortality rate among gynecological malignancies (3).Photodynamic therapy (PDT) has garnered attention as a novel therapy to reduce the tumor burden on a patient. PDT has been used to treat superficial esophageal cancer, early lung cancer and early gastric cancer (4-6). In gynecology, PDT has been used to treat early cancer of the cervix (7). Younger patients tend to opt to receive treatment that preserves fertility, and PDT may be such a treatment (7). Therefore, attention has focused on the usefulness of PDT in that regard. Unlike conventional approaches, PDT leaves the cervix intact, has a high cure rate, and does not hamper pregnancy or delivery following surgery (7).PDT is a therapy involving photosensitizers (or their precursors) with an affinity for tumors. The sp...

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Section: Signal -------------------------------------------------------supporting

confidence: 94%

Differences in the sensitivity of ovarian cancer to photodynamic therapy and the mechanisms for those differences

et al. 2017

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“…Recently, a role for insect GSTs in mediating the oxidative stress response has been suggested by a number of studies (eg Yan et al ., ; Meng et al ., ). For example, in venom glands of Apis mellifera , proteomic analysis indicated that the presence of GSTs seems to defend against oxidative stress (Peiren et al ., ).…”

Section: Introductionmentioning

confidence: 97%

“…The number of Cys residues that each GSTO protein contains varies within species. For instance, human GSTO2 has 11 Cys residues compared with five in GSTO1 (Zhou et al ., ), whereas Apis cerana cerana GSTO1 and GSTO2 both have three Cys residues (Meng et al ., ). Several studies have demonstrated that the site‐directed mutagenesis of active site Cys residues can result in undetected or decreased enzymatic activity toward GSTOs (Burmeister et al ., ; Yamamoto et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Functional and mutational analyses of an omega‐class glutathione S‐transferase (GSTO2) that is required for reducing oxidative damage in Apis cerana cerana

Zhang

Liu

et al. 2016

Insect Molecular Biology

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Glutathione S-transferases perform a variety of vital functions, particularly in reducing oxidative damage. Here, we investigated the expression patterns of Apis cerana cerana omega-class glutathione S-transferase 2 (AccGSTO2) under various stresses and explored its connection with antioxidant defences. We found that AccGSTO2 knockdown by RNA interference triggered increased mortality in Ap. cerana cerana, and immunohistochemistry revealed significantly decreased AccGSTO2 expression, particularly in the midgut and fat body. Further analyses indicated that AccGSTO2 knockdown resulted in decreases in catalase and glutathione reductase activities, ascorbate content and the ratio of reduced to oxidized glutathione, and increases in H2 O2 , malondialdehyde and carbonyl contents. We also analysed the transcripts of other antioxidant genes and found that many genes were down-regulated in the AccGSTO2 knockdown samples, revealing that AccGSTO2 may be indispensable for attaining a normal lifespan by enhancing cellular oxidative resistance. In addition, the roles of cysteine residues in AccGSTO2 were explored using site-directed mutagenesis. Mutants of Cys(28) and Cys(124) significantly affected the enzyme and antioxidant activities of AccGSTO2, which may be attributed to the changes in the spatial structures of mutants as determined by homology modelling. In summary, these observations provide novel insight into the structural and functional characteristics of GSTOs.

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“…5A-D). Some of those genes belong to the thioredoxin family, such as Trx-1, Trx1-like2 and Trxr-1, as well as the glutaredoxin and glutathione families, all known to be involved with Apis cerana's response to oxidative stress (Meng et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

RNA-seq reveals disruption in honey bee gene regulation when caged and deprived of hive conditions

Alburaki¹,

Karim

Lamour

et al. 2019

Journal of Experimental Biology

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In this study, we present phenotypic and genetic data characterizing the impact of imidacloprid and caging stress on honey bee Apis mellifera physiological responses and regulation of 45 genes using targeted-RNA seq. The term 'caging stress' characterizes the effects of depriving honey bees of all hive aspects and conditions. Two cohorts of 1 day old sister bees were subjected to different conditions. One cohort was caged and fed different imidacloprid-tainted sugar solutions and the second was marked and introduced back to its natal hive. Physiological bee parameters and diet behavior were monitored daily for caged bees over several weeks. Bee samples from both cohorts were sampled weekly for RNA sequencing and oxidative stress analyses. Imidacloprid induced significant protein damage and post-ingestive aversion responses in caged bees, leading to lower tainted syrup consumption and higher water intake compared with the controls. No differentially expressed genes were observed among caged bees in regards to imidacloprid treatment. However, significant upregulation in antioxidant genes was recorded in caged bees as compared with hive bees, with overwhelming downregulation in all gene categories in caged bees at week 4. We identified two sets of genes that were constantly regulated in caged bees, including Rsod with unknown function in insects that could potentially characterize caging stress in honey bees.

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Characterization and Mutational Analysis of Omega-Class GST (GSTO1) from Apis cerana cerana, a Gene Involved in Response to Oxidative Stress

Cited by 41 publications

References 52 publications

Differences in the sensitivity of ovarian cancer to photodynamic therapy and the mechanisms for those differences

Differences in the sensitivity of ovarian cancer to photodynamic therapy and the mechanisms for those differences

Functional and mutational analyses of an omega‐class glutathione S‐transferase (GSTO2) that is required for reducing oxidative damage in Apis cerana cerana

RNA-seq reveals disruption in honey bee gene regulation when caged and deprived of hive conditions

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