The role of PKCζ in amikacin-induced apoptosis in the cochlea: Prevention by aspirin

Lecain, Éric; Omri, Boubaker; Huy, P. Tran Ba; Crisanti, Patricia

doi:10.1007/s10495-006-0580-0

Cited by 13 publications

(10 citation statements)

References 67 publications

(82 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the lateral line, aminoglycoside-induced hair cell death is independent of caspase activation, implicating this caspase-independent role of Xiap in gentamicin damage ( Coffin et al, 2013b ). AIF translocates from the mitochondria to the nucleus in damaged cells, and AIF translocation is reported in hair cells in response to amikacin administration in vivo or to gentamicin in vitro , suggesting that AIF may mediate hair cell damage ( Lecain et al, 2007 ; Zhang et al, 2012 ). However, an in vivo study in mice did not find AIF translocation after kanamycin ototoxicity, but did note a decrease in cochlear AIF expression ( Jiang et al, 2006a ).…”

Section: Discussionmentioning

confidence: 99%

PI3K and Inhibitor of Apoptosis Proteins Modulate Gentamicin- Induced Hair Cell Death in the Zebrafish Lateral Line

Wiedenhoft

Hayashi

Coffin

2017

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Inner ear hair cell death leads to sensorineural hearing loss and can be a direct consequence of aminoglycoside antibiotic treatment. Aminoglycosides such as gentamicin are effective therapy for serious Gram-negative bacterial infections such as some forms of meningitis, pneumonia, and sepsis. Aminoglycosides enter hair cells through mechanotransduction channels at the apical end of hair bundles and initiate intrinsic cell death cascades, but the precise cell signaling that leads to hair cell death is incompletely understood. Here, we examine the cell death pathways involved in aminoglycoside damage using the zebrafish (Danio rerio). The zebrafish lateral line contains hair cell-bearing organs called neuromasts that are homologous to hair cells of the mammalian inner ear and represents an excellent model to study ototoxicity. Based on previous research demonstrating a role for p53, Bcl2 signaling, autophagy, and proteasomal degradation in aminoglycoside-damaged hair cells, we used the Cytoscape GeneMANIA Database to identify additional proteins that might play a role in neomycin or gentamicin ototoxicity. Our bioinformatics analysis identified the pro-survival proteins phosphoinositide-dependent kinase-1 (PDK1) and X-linked inhibitor of apoptosis protein (Xiap) as potential mediators of gentamicin-induced hair cell damage. Pharmacological inhibition of PDK1 or its downstream mediator protein kinase C facilitated gentamicin toxicity, as did Xiap mutation, suggesting that both PI3K and endogenous Xiap confer protection. Surprisingly, aminoglycoside-induced hair cell death was highly attenuated in wild type Tupfel long-fin (TL fish; the background strain for the Xiap mutant line) compared to wild type ∗AB zebrafish. Pharmacologic manipulation of p53 suggested that the strain difference might result from decreased p53 in TL hair cells, allowing for increased hair cell survival. Overall, our studies identified additional steps in the cell death cascade triggered by aminoglycoside damage, suggesting possible drug targets to combat hearing loss resulting from aminoglycoside exposure.

show abstract

Section: Discussionmentioning

confidence: 99%

PI3K and Inhibitor of Apoptosis Proteins Modulate Gentamicin- Induced Hair Cell Death in the Zebrafish Lateral Line

Wiedenhoft

Hayashi

Coffin

2017

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…ASA prevents cleavage of PKC zeta, a key regulator of NF κβ activated by exposure to amikacin [199]. Systemic administration of ASA effectively protects guinea pigs from gentamicin-induced hearing loss [200].…”

Section: Efforts In Hair Cell Protectionmentioning

confidence: 99%

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Huth

Ricci

Cheng

2011

International Journal of Otolaryngology

324

302

View full text Add to dashboard Cite

Aminoglycosides are commonly prescribed antibiotics with deleterious side effects to the inner ear. Due to their popular application as a result of their potent antimicrobial activities, many efforts have been undertaken to prevent aminoglycoside ototoxicity. Over the years, understanding of the antimicrobial as well as ototoxic mechanisms of aminoglycosides has increased. These mechanisms are reviewed in regard to established and potential future targets of hair cell protection.

show abstract

“…Numerous in vivo and in vitro studies have demonstrated that Amikacin caused hair cell death and aberration of hearing thresholds and/or hearing levels [ 28 29 30 31 32 33 34 35 36 37 ]. In our study, group 1 (AK) had significant decreases of DPOAE amplitudes on days 7 and 15 as compared to initial DPOAE amplitudes, and our findings are compatible with relevant literature.…”

Section: Discussionmentioning

confidence: 99%

“…Studies with numerous agents were conducted in recent years in search of a prevention for amikacin-induced ototoxicity [ 28 29 30 31 32 33 34 35 36 37 ] ( Table 2 ). Research on this issue was accelerated especially during the last decade, but currently there is no agent in use (for counteracting AK's ototoxic effects) that has achieved general consensus.…”

Section: Discussionmentioning

confidence: 99%

An Evaluation of the Protective Effects of Thymoquinone on Amikacin-Induced Ototoxicity in Rats

Aksoy

Doğan

Özturan

et al. 2015

Clin Exp Otorhinolaryngol

View full text Add to dashboard Cite

ObjectivesIn this study we investigated the probable protective effects of thymoquinone on amikacin-induced ototoxicity in rats.MethodsThirty-two healthy rats were divided into four groups (amikacin, amikacin+thymoquinone, thymoquinone, and no treatment). Thymoquinone was fed to the rats via oral gavage in a dose of 40 mg/kg/day throughout the study period of 14 days. Amikacin was given by the intramuscular route in a dose of 600 mg/kg/day. Audiological assessment was conducted by the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) tests, administered to all rats at the beginning of the study, and also on days 7 and 15. Biochemical parameters were calculated at the termination of the study to evaluate the oxidative status.ResultsThere were significant decreases in DPOAE values and significant increases in ABR thresholds of the amikacin group on days 7 and 15, as compared to the amikacin+thymoquinone group. While ABR thresholds of the amikacin group increased significantly on days 7 and 15 as compared to their initial values, there were no significant differences between the initial and the 7th and 15th day values of ABR thresholds in the amikacin+thymoquinone group. Total oxidant status and oxidative stress index values of the amikacin+thymoquinone group were significantly lower than those of the amikacin group. Total antioxidant status values of the amikacin+thymoquinone group were significantly higher than those of the amikacin group.ConclusionOur study has demonstrated that the ototoxic effect brought forth by amikacin could be overcome with the concurrent use of thymoquinone.

show abstract

The role of PKCζ in amikacin-induced apoptosis in the cochlea: Prevention by aspirin

Cited by 13 publications

References 67 publications

PI3K and Inhibitor of Apoptosis Proteins Modulate Gentamicin- Induced Hair Cell Death in the Zebrafish Lateral Line

PI3K and Inhibitor of Apoptosis Proteins Modulate Gentamicin- Induced Hair Cell Death in the Zebrafish Lateral Line

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

An Evaluation of the Protective Effects of Thymoquinone on Amikacin-Induced Ototoxicity in Rats

Contact Info

Product

Resources

About