Previous reports have implicated Otos, a novel specific gene expressed by spiral ligament fibrocytes (SLFs) with unclear functions, as a protective gene for cochlea. However, whether Otos gene could protect SLFs against cisplatin (DDP)-induced apoptosis remains largely unknown. In the present study, we utilized Adenoviral-mediated gene transfection to up-regulate Otos expression in cultured SLFs and further assessed the cell viability and apoptosis as well as possible MAPK and mitochondrial pathways. As expected, the data showed that Otos up-regulation significantly decreased apoptosis of SLFs induced by DDP possibly through activation of ERK and partial inhibition of JNK and mitochondrial pathway but not p-38 pathway, suggesting Otos as a potential protective gene for cochlea and raising the possibility of Otos up-regulation as a promising approach to DDP-induced deafness therapy.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.tox.2008.03.004 | DOI Listing |
Clin Cancer Res
July 2019
Department of Medicine, University of Chicago, Chicago, Illinois.
Purpose: Cisplatin, a commonly used chemotherapeutic, results in tinnitus, the phantom perception of sound. Our purpose was to identify the clinical and genetic determinants of tinnitus among testicular cancer survivors (TCS) following cisplatin-based chemotherapy.
Experimental Design: TCS ( = 762) were dichotomized to cases (moderate/severe tinnitus; = 154) and controls (none; = 608).
J Am Chem Soc
November 2017
Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
Peptide hormones are attractive as injectable therapeutics and imaging agents, but they often require extensive modification by mutagenesis and/or chemical synthesis to prevent rapid in vivo degradation. Alternatively, the single-atom, O-to-S modification of peptide backbone thioamidation has the potential to selectively perturb interactions with proteases while preserving interactions with other proteins, such as target receptors. Here, we use the validated diabetes therapeutic, glucagon-like peptide-1 (GLP-1), and the target of clinical investigation, gastric inhibitory polypeptide (GIP), as proof-of-principle peptides to demonstrate the value of thioamide substitution.
View Article and Find Full Text PDFToxicology
June 2008
Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Previous reports have implicated Otos, a novel specific gene expressed by spiral ligament fibrocytes (SLFs) with unclear functions, as a protective gene for cochlea. However, whether Otos gene could protect SLFs against cisplatin (DDP)-induced apoptosis remains largely unknown. In the present study, we utilized Adenoviral-mediated gene transfection to up-regulate Otos expression in cultured SLFs and further assessed the cell viability and apoptosis as well as possible MAPK and mitochondrial pathways.
View Article and Find Full Text PDFMol Cell Biol
January 2005
INSERM U.583, Physiopathologie et Thérapie des Déficits Sensoriels et Moteurs, Institut des Neurosciences de Montpellier, Hôpital Saint-Eloi, BP 74103, 80, rue Augustin Fliche, 34295 Montpellier cedex 05, France.
In the cochlea, the mammalian auditory organ, fibrocytes of the mesenchymal nonsensory regions play important roles in cochlear physiology, including the maintenance of ionic and hydric components in the endolymph. Occurrence of human deafness in fibrocyte alterations underlines their critical roles in auditory function. We recently described a novel gene, Otos, which encodes otospiralin, a small protein of unknown function that is produced by the fibrocytes of the cochlea and vestibule.
View Article and Find Full Text PDFNeurogenetics
April 2003
Physiopathologie et Thérapie des Déficits Sensoriels et Moteurs, INSERM U 583, 71 rue de Navacelles, 34090 Montpellier, France.
Otospiralin is a novel protein of unknown function that is produced by non-sensory cells (fibrocytes) of the inner ear (cochlea and vestibule). We showed that downregulation of otospiralin in guinea pigs leads to deafness and we therefore hypothesized that genetic defects in the otospiralin gene could also cause deafness in humans. In this study, we cloned and localized OTOSP, the human gene for otospiralin.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!