Genetic susceptibility to aminoglycoside ototoxicity

Nguyên, Tiên Hiêp; Jeyakumar, Anita

doi:10.1016/j.ijporl.2019.02.002

Cited by 43 publications

(35 citation statements)

References 30 publications

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“…The similarities in the chemical structure of aminoglyco sides sometimes lead to confusion (as it happened with gentamicin B1 [121] antibiotics of this type are presumably bacteriospecific due to the structural features of the helix h44 in the eukaryotic DC [14,110,122,123]. However, this does not make them safe for eukaryotic cells, as they can sup press mitochondrial protein synthesis and cause severe side effects (primarily nephro and ototoxicity), which limits their use as antibacterial drugs [124,125]. As men tioned above, some aminoglycosides also inhibit translo cation at elevated concentrations.…”

Section: Inhibitors Of Eukaryotic Ribosomementioning

confidence: 99%

A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis

Dmitriev

Vladimirov

Lashkevich

2020

Biochemistry Moscow

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Eukaryotic ribosome and cap-dependent translation are attractive targets in the antitumor, antiviral, anti-inflammatory, and antiparasitic therapies. Currently, a broad array of small-molecule drugs is known that specifically inhibit protein synthesis in eukaryotic cells. Many of them are well-studied ribosome-targeting antibiotics that block translocation, the peptidyl transferase center or the polypeptide exit tunnel, modulate the binding of translation machinery components to the ribosome, and induce miscoding, premature termination or stop codon readthrough. Such inhibitors are widely used as anticancer, anthelmintic and antifungal agents in medicine, as well as fungicides in agriculture. Chemicals that affect the accuracy of stop codon recognition are promising drugs for the nonsense suppression therapy of hereditary diseases and restoration of tumor suppressor function in cancer cells. Other compounds inhibit aminoacyl-tRNA synthetases, translation factors, and components of translation-associated signaling pathways, including mTOR kinase. Some of them have antidepressant, immunosuppressive and geroprotective properties. Translation inhibitors are also used in research for gene expression analysis by ribosome profiling, as well as in cell culture techniques. In this article, we review well-studied and less known inhibitors of eukaryotic protein synthesis (with the exception of mitochondrial and plastid translation) classified by their targets and briefly describe the action mechanisms of these compounds. We also present a continuously updated database (http://eupsic.belozersky.msu.ru/) that currently contains information on 370 inhibitors of eukaryotic protein synthesis.

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Section: Inhibitors Of Eukaryotic Ribosomementioning

confidence: 99%

A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis

Dmitriev

Vladimirov

Lashkevich

2020

Biochemistry Moscow

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“…[ 5 , 60 ] If culture confirms GBS, amoxicillin/ampicillin is recommended, and gentamicin should be discontinued after 48 h to prevent cumulative nephro- and oto-toxicity. [ 61 , 62 ] In case of ampicillin-resistant E. coli infection, a third-generation cephalosporin like cefotaxime should be used (100 mg/kg per day), and at a higher dosage (200 mg/kg per day) when meningitis is suspected. In case of hospital-acquired LOS which is often caused by CoNS like Staphylococcus epidermidis , [ 42 ] vancomycin by intravenous injection (or continuous infusion through a CVC if it is infected) is recommended at first, [ 63 , 64 ] as many of CoNS are indeed methicillin-resistant.…”

Section: Empirical Treatment Of Neonatal Sepsismentioning

confidence: 99%

Neonatal sepsis: within and beyond China

Dong

Basmaci

Titomanlio

et al. 2020

Chinese Medical Journal

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“…This transition makes the human mitochondrial ribosome more bacteria-like, and consequently alters binding sites for aminoglycoside antibiotics (AmAn) [7]. Thus, screening the two primary mutations of deafness in general population is important for genetic counseling and disease prevention [8]. To date, several molecular methods have been designed for detecting the deafness-associated gene mutations, such as denaturing high-performance liquid chromatography (DHPLC) [9], SNaPshot mini-sequencing technology [10], amplification refractory mutation system PCR (ARMS-PCR) [11] and PCR-Sanger sequencing.…”

Section: Introductionmentioning

confidence: 99%

Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method

et al. 2020

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Mitochondrial 12S rRNA A1555G and C1494T mutations are the major contributors to hearing loss. As patients with these mutations are sensitive to aminoglycosides, mutational screening for 12S rRNA is therefore recommended before the use of aminoglycosides. Most recently, we developed a novel multiplex allele-specific PCR (MAS-PCR) that can be used for detecting A1555G and C1494T mutations. In the present study, we employed this MAS-PCR to screen the 12S rRNA mutations in 500 deaf patients and 300 controls from 5 community hospitals. After PCR and electrophoresis, two patients with A1555G and one patient with C1494T were identified, this was consistent with Sanger sequence results. We further traced the origin of three Chinese pedigrees. Clinical evaluation revealed variable phenotypes of hearing loss including severity, age at onset and audiometric configuration in these patients. Sequence analysis of the mitochondrial genomes from matrilineal relatives suggested the presence of three evolutionarily conserved mutations: tRNACys T5802C, tRNALys A8343G and tRNAThr G15930A, which may result the failure in tRNAs metabolism and lead to mitochondrial dysfunction that was responsible for deafness. However, the lack of any functional variants in GJB2, GJB3, GJB6 and TRMU suggested that nuclear genes may not play active roles in deafness expression. Hence, aminoglycosides and mitochondrial genetic background may contribute to the clinical expression of A1555G/C1494T-induced deafness. Our data indicated that the MAS-PCR was a fast, convenience method for screening the 12S rRNA mutations, which was useful for early detection and prevention of mitochondrial deafness.

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Genetic susceptibility to aminoglycoside ototoxicity

Cited by 43 publications

References 30 publications

A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis

A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis

Neonatal sepsis: within and beyond China

Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method

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