Hydrogen‐rich water regulates effects of ROS balance on morphology, growth and secondary metabolism via glutathione peroxidase in <i>Ganoderma lucidum</i>

Ren, Ang; Liu, Rui; Miao, Zhigang; Zhang, Xue; Cao, Pengfei; Chen, Tianxi; Li, Chen-Yang; Shi, Liang; Jiang, Ailiang; Zhao, Mingwen

doi:10.1111/1462-2920.13498

Cited by 60 publications

(38 citation statements)

References 61 publications

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“…Detection and measurement of GA and its mesostate in the GA biosynthesis pathway. GAs, squalene, and lanosterol were extracted and measured from fungal mycelia according to a previously described method (37). Ganoderic acid-a was used as the standard (38).…”

Section: Methodsmentioning

confidence: 99%

Cross Talk between Nitric Oxide and Calcium-Calmodulin Regulates Ganoderic Acid Biosynthesis in Ganoderma lucidum under Heat Stress

Shi

Zhu

et al. 2018

Appl Environ Microbiol

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We previously reported that high temperature impacts ganoderic acid (GA) biosynthesis in () via Ca Therefore, to further understand the signal regulating network of the organism's response to heat stress (HS), we examined the role of nitric oxide (NO) under HS. After HS treatment, the NO level was significantly increased by 120% compared with that under the control conditions. The application of a NO scavenger resulted in a 25% increase in GA compared with that found in the sample treated only with HS. Additionally, application of a NO donor to increase NO resulted in a 30% lower GA content than that in the sample treated only with HS. These results show that the increase in NO alleviates HS-induced GA accumulation. Subsequently, we aimed to detect the effects of the interaction between NO and Ca on GA biosynthesis under HS in Our pharmacological approaches revealed that the NO and Ca signals promoted each other in response to HS. We further constructed the silenced strain of nitrate reductase (NR) and calmodulin (CaM), and the results are in good agreement with the silenced strain and pharmacological experiment. The cross-promotion between NO and Ca signals is involved in the regulation of HS-induced GA biosynthesis in , and this finding is supported by studies with NRi and CaMi strains. However, Ca may have a more direct and significant effects on the HS-induced GA increase than NO. These data indicate that NO functions in signaling and has a close relationship with Ca in HS-induced GA biosynthesis. HS is an important environmental stress affecting the growth and development of organisms. We previously reported that HS modulates GA biosynthesis in via Ca However, the signal regulating network of the organism's response to HS has not yet been elucidated. In this study, we found that NO relieved HS-induced GA accumulation, and NO and Ca could exert promoting effects on each other in response to HS. Further research on the effect of NO and Ca on the production of GAs in response to HS indicated that Ca has a notably more direct and significant effect on the HS-induced GA increase than NO. Our results improve our understanding of the mechanism of HS signal transduction in fungi. A greater understanding of the regulation of secondary metabolism in response to environmental stimuli will provide clues regarding the role of these products in fungal biology.

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Section: Methodsmentioning

confidence: 99%

Cross Talk between Nitric Oxide and Calcium-Calmodulin Regulates Ganoderic Acid Biosynthesis in Ganoderma lucidum under Heat Stress

Shi

Zhu

et al. 2018

Appl Environ Microbiol

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“…Thus, enhancing the content of GA is important and urgently needed to be solved. The growth of G. lucidum and the synthesis of SMs are affected by a variety of environmental factors, such as nutrients, chemical inducement and physical stresses (Shi et al, 2015;Liu et al, 2017;Ren et al, 2017;Liu et al, 2018a). Among these factors, nitrogen plays a special role in the biosynthesis of SMs, and changes of nitrogen sources or the C/N ratio could result in an enhancement of GA (Hsieh and Yang, 2004;Zhao et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Dual functions of AreA, a GATA transcription factor, on influencing ganoderic acid biosynthesis in Ganoderma lucidum

Zhu

Sun

Shi

et al. 2019

Environmental Microbiology

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Summary Nitrogen metabolism repression (NMR) has been well studied in filamentous fungi, but the molecular mechanism of its effects on fungal secondary metabolism has been generally unexplored. Ganoderic acid (GA) biosynthesis in Ganoderma lucidum differs between ammonia and nitrate nitrogen sources. To explain the functions of NMR in secondary metabolism, AreA, which is a core transcription factor of NMR, was characterized in G. lucidum. The transcription level of AreA was dramatically increased (approximately 4.5‐folds), with the nitrate as the sole nitrogen source, compared with that with ammonia as the source. In addition, the expression of related genes involved in NMR was changed (upregulated of MeaB and downregulated of Nmr and GlnA) when AreA was knockdown. Yeast one‐hybrid and electrophoretic mobility shift assay results showed that AreA could directly bind to the promoter of fps (encoding farnesyl‐diphosphate synthase) to activate its expression. However, GA biosynthesis was increased (27% in the ammonia source and 77% in the nitrate source) in AreAi mutant strains versus that in control strains. These results showed that another important factor must participate in regulating GA biosynthesis other than the direct activation of AreA. Furthermore, we found that the content of nitric oxide (NO) was increased approximately 2.7‐folds in the nitrate source compared with that in the ammonia. By adding the NO donor (SNP) or scavenger (cPTIO) and using NR‐silenced or NR‐overexpressed strains, we found that there was a negative correlation between the NO contents and GA biosynthesis. NO generated by nitrate reductase (NR) during the nitrogen utilization burst and could negatively influence GA biosynthesis. As a global transcription factor, AreA could also regulate the expression of NR. Our studies provide novel insight into the dual functions of AreA in GA biosynthesis during nitrogen assimilation.

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“…Therefore, reducing GSH and thioredoxin pool in cancer cells, through the inhibition of GR and TrxR enzymes, may be considered as an effective strategy to combat these tumor cells by altering their ability to eliminate ROS and to cope with oxidative damage. Both glutathioneand thioredoxin-dependent systems require NADPH, as cofactor, to combat ROS generated from oxidative stress [9]. It has been systematically showed that NADPH is a limiting factor for oxidative stress management in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species-Mediated Apoptosis and Cytotoxicity of Newly Synthesized Pyridazin-3-Ones In P815 (Murin Mastocytoma) Cell Line

et al. 2019

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Background In cancer cells, the intracellular antioxidant capacity and the redox homeostasis are mainly maintained by the glutathione- and thioredoxin-dependent systems which are considered as promising targets for anticancer drugs. Pyridazinones constitute an interesting source of heterocyclic compounds for drug discovery. The present investigation focused on studying the in-vitro antitumor activity of newly synthesized Pyridazin-3(2h)-ones derivatives against P815 (Murin mastocytoma) cell line. Methods The in-vitro cytotoxic activities were investigated toward the P815 cell line using tetrazolium-based MTT assay. Lipid peroxidation and the specific activities of antioxidant enzymes were also determined. Results The newly compounds had a selective dose-dependent cytotoxic effect without affecting normal cells (PBMCs). Apoptosis was further confirmed through the characteristic apoptotic morphological changes and DNA fragmentation. Two compounds (6f and 7h) were highly cytotoxic and were submitted to extend biological testing to determine the likely mechanisms of their cytotoxicity. Results showed that these molecules may induce cytotoxicity via disturbing the redox homeostasis. Importantly, the anticancer activity of 6f and 7h could be due to the intracellular reactive oxygen species hypergeneration through significant loss of glutathione reductase and thioredoxin reductase activities. This eventually leads to oxidative stress-mediated P815 cell apoptosis. Furthermore, the co-administration of 6f or 7h with Methotrexate exhibited a synergistic cytotoxic effect. Conclusions considering their significant anticancer activity and chemosensitivity, 6f and 7h may improve the therapeutic efficacy of the current treatment for cancer.

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Hydrogen‐rich water regulates effects of ROS balance on morphology, growth and secondary metabolism via glutathione peroxidase in Ganoderma lucidum

Cited by 60 publications

References 61 publications

Cross Talk between Nitric Oxide and Calcium-Calmodulin Regulates Ganoderic Acid Biosynthesis in Ganoderma lucidum under Heat Stress

Cross Talk between Nitric Oxide and Calcium-Calmodulin Regulates Ganoderic Acid Biosynthesis in Ganoderma lucidum under Heat Stress

Dual functions of AreA, a GATA transcription factor, on influencing ganoderic acid biosynthesis in Ganoderma lucidum

Reactive Oxygen Species-Mediated Apoptosis and Cytotoxicity of Newly Synthesized Pyridazin-3-Ones In P815 (Murin Mastocytoma) Cell Line

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