Role of conserved nucleotides in building the 16S rRNA binding site ofE.coliribosomal protein S8

Abstract Background Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown. Methods We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment. Results 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity. Conclusions This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.

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Superinduction of CYP1A1 transcription by cycloheximide. Role of the DNA binding site for the liganded Ah receptor.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)42158-8 ◽

1992 ◽

Vol 267 (21) ◽

pp. 15146-15151

Author(s):

A Lusska ◽

L Wu ◽

J P Whitlock

Keyword(s):

Dna Binding ◽

Binding Site ◽

Ah Receptor ◽

Dna Binding Site

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Excision and transposition of Tn5 as an SOS activity in Escherichia coli.

Genetics ◽

10.1093/genetics/128.1.45 ◽

1991 ◽

Vol 128 (1) ◽

pp. 45-57 ◽

Cited By ~ 1

Author(s):

C T Kuan ◽

S K Liu ◽

I Tessman

Keyword(s):

Escherichia Coli ◽

Binding Site ◽

Reca Protein ◽

Precursor Molecule ◽

Functional Integrity ◽

Lexa Protein ◽

Lexa Binding ◽

Additional Role ◽

Stimulation Of

Abstract Excision and transposition of the Tn5 element in Escherichia coli ordinarily appear to occur by recA-independent mechanisms. However, recA(Prtc) genes, which encode RecA proteins that are constitutively activated to the protease state, greatly enhanced excision and transposition; both events appeared to occur concomitantly and without destruction of the donor DNA. The recombinase function of the RecA protein was not required. Transposition was accompanied by partial, and occasionally full, restoration of the functional integrity of the gene vacated by the excised Tn5. The stimulation of transposition was inhibited by an uncleavable LexA protein and was strongly enhanced by an additional role of the RecA(Prtc) protein besides its mediation of LexA cleavage. To account for the enhanced transposition, we suggest that (i) there may be a LexA binding site within the promoter for the IS50 transposase, (ii) activated RecA may cleave the IS50 transposition inhibitor, and (iii) the transposase may be formed by RecA cleavage of a precursor molecule.

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