Free Radicals and Reactive Oxygen Species

Siraki, Arno G.

doi:10.1016/b978-0-12-801238-3.01895-x

Cited by 15 publications

(4 citation statements)

References 246 publications

(127 reference statements)

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“…Rv1453 protein can bind to the qor gene and inhibit the expression of quinone oxidoreductase (QOR) ( 14 ). QOR in M. tuberculosis catalyzes the two-electron reduction of quinone to hydroquinone to prevent the generation of free radicals during redox, and transfers reducing equivalents to the electron transport chain, which is vital for energy production ( 33 ). We speculate that the C-17T mutation in the Rv1453 intergenic, downregulated the expression of the Rv1453 gene.…”

Section: Discussionmentioning

confidence: 99%

Rv1453 is associated with clofazimine resistance in Mycobacterium tuberculosis

Zhang,

et al. 2023

Microbiol Spectr

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Clofazimine (CFZ) has been repurposed for treating tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB). However, the mechanisms of resistance to clofazimine are poorly understood. We previously reported a mutation located in the intergenic region of Rv1453 that was linked to resistance to CFZ and demonstrated that an Rv1453 knockout resulted in an increased minimum inhibitory concentration (MIC) of CFZ. The current study aims to go back and describe in detail how the mutation was identified and further explore its association with CFZ resistance by testing additional 30 isolates. We investigated MICs of clofazimine against 100 clinical strains isolated from MDR-TB patients by microplate alamarBlue assay. Whole-genome sequencing (WGS) was performed on 11 clofazimine-resistant and 7 clofazimine-susceptible strains, including H37Rv. Among the 11 clofazimine-resistant mutants subjected to WGS, the rate of mutation in the intergenic region of the Rv1453 gene was 55% (6/11) in clofazimine-resistant strains. Among another 30 clofazimine-resistant clinical isolates, 27 had mutations in the intergenic region of the Rv1453 gene. A mutation in the Rv1453 gene associated with clofazimine resistance was identified, which shed light on the mechanisms of action and resistance of clofazimine. IMPORTANCE Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis , especially the emergence of multidrug-resistant tuberculosis (MDR-TB) brings great distress to humans. Clofazimine (CFZ) plays an important role in the treatment of MDR-TB. To understand the underlying mechanism of clofazimine resistance better, in this study, we review and detail the findings of the mutation of intergenic region of Rv1453 and find additional evidence that this mutation is related to clofazimine resistance in 30 additional isolates. The significance of our research is to contribute to a comprehensive understanding of clofazimine-resistant mechanisms, which is critical for reducing the emergence of resistance and for anti-TB drug discovery.

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Section: Discussionmentioning

confidence: 99%

Rv1453 is associated with clofazimine resistance in Mycobacterium tuberculosis

Zhang,

et al. 2023

Microbiol Spectr

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“…Quinone reductase can directly catalyze the two electrons reduction of quinone to hydroquinone, preventing free radical generation during redox by avoiding the one electron reduction of quinone to the semiquinone. 14 And, it has been reported that lpdA gene, which also encodes quinone reductase, can scavenge reactive oxygen species and reduce the oxidative stress in M. tuberculosis . 27 , 28 Inhibition of quinone oxidoreductase activity can increase free radical damage.…”

Section: Discussionmentioning

confidence: 99%

The Transcription Factor Rv1453 Regulates the Expression of qor and Confers Resistant to Clofazimine in Mycobacterium tuberculosis

Li¹,

Fu²,

Zhang³

et al. 2021

IDR

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Objective Clofazimine plays an important role in the treatment of drug-resistant tuberculosis. However, the mechanism of clofazimine resistance remains unclear. In order to slow down the occurrence of clofazimine resistance, it is necessary to study its resistance mechanism. Methods In this study, we constructed Rv1453 knockout, complementary and overexpressed strain. The minimum inhibitory concentration (MIC) of clofazimine against Mycobacterium tuberculosis was detected by microplate alamar blue assay (MABA). The transcription levels of Rv1453 and its adjacent genes were detected by quantitative reverse transcriptase PCR. The purified Rv1453 protein was used for electrophoretic mobility shift assay (EMSA) to identify the binding site of Rv1453 protein. Results The minimum inhibitory concentration (MIC) of clofazimine increased about 4-fold for the Rv1453 knockout strain and decreased about 4-fold for the Rv1453 overexpressed strain compared with Mycobacterium tuberculosis H37Rv. Further analysis showed that Rv1453 protein, as a regulatory protein, binds to the RNA polymerase binding site of qor and blocks the transcription process. Conclusion This study preliminarily revealed that Rv1453 protein of Mycobacterium tuberculosis affects its susceptibility to clofazimine by regulating the transcription level of qor, which is shedding a new light on the mechanism of clofazimine resistance.

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“…Radikal bebas merupakan atom atau molekul yang mengandung satu atau lebih elektron yang tidak berpasangan. Radikal dapat bermuatan atau tidak bermuatan [10]. Satu molekul antioksidan dapat bereaksi dengan radikal bebas tunggal dan mampu menetralkan radikal bebas dengan menyumbangkan satu elektronnya [11,12].…”

Section: Pendahuluanunclassified

Profil Fitokimia dan Aktivitas Antioksidan Beberapa Tumbuhan Genus Artocarpus di Indonesia

et al. 2021

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Artocarpus merupakan tumbuhan genus utama keluarga Moraceae dengan jumlah spesies hampir 1.400. Beberapa spesies dari genus tersebut dapat dimanfaatkan sebagai makanan dan obat tradisional di Asia Tenggara, termasuk Indonesia. Jenis yang banyak tumbuh di Indonesia yaitu Artocarpus altilis (sukun), Artocarpus camansi (kluwih), Artocarpus heterophyllus (nangka), Artocarpus integer (cempedak), dan Artocarpus odoratissimus (tarap). Tumbuhan tersebut memiliki potensi sebagai bahan obat dan punya nilai gizi yang tinggi. Review ini bertujuan untuk mengkaji perbedaan antar spesies, profil fitokimia, dan aktivitasnya sebagai antioksidan dari kelima tumbuhan tersebut. Narrative review ini ditulis berdasarkan penelusuran literatur yang berupa publikasi artikel penelitian yang ada di basis data Google Scholar, PubMed, dan Science Direct. Selain itu digunakan sumber pustaka lain berupa buku dan naskah tugas akhir untuk memperkaya isi artikel. Hasil kajian literatur terhadap 5 tumbuhan tersebut menunjukkan bahwa beberapa tumbuhan memiliki kemiripan morfologi daun walaupun secara fisik masih bisa dibedakan. Profil fitokimianya memiliki keunikan dengan kandungan utama berupa senyawa fenolik termasuk flavonoid, stilbenoid, arilbenzofuron, dan neolignan yang tersebar pada bagian daun, buah, bunga, dan kulit. Keunikan tersebut ditemui dengan adanya senyawa golongan flavonoid terprenilasi dan tergeranilasi. Senyawa fenolik tersebut mempunyai kemampuan sebagai antioksidan pada beberapa model uji dan potensial untuk dikembangakan sebagai antioksidan atau kandidat obat terutama untuk penyakit yang melibatkan mekanisme radikal bebas dalam mekanisme patofisiologinya.

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Free Radicals and Reactive Oxygen Species

Cited by 15 publications

References 246 publications

Rv1453 is associated with clofazimine resistance in Mycobacterium tuberculosis

Rv1453 is associated with clofazimine resistance in Mycobacterium tuberculosis

The Transcription Factor Rv1453 Regulates the Expression of qor and Confers Resistant to Clofazimine in Mycobacterium tuberculosis

Profil Fitokimia dan Aktivitas Antioksidan Beberapa Tumbuhan Genus Artocarpus di Indonesia

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