Int J Mol Sci
February 2024
Nucleotide excision repair (NER) is a multistep biochemical process that maintains the integrity of the genome. Unlike other mechanisms that maintain genomic integrity, NER is distinguished by two irreversible nucleolytic events that are executed by the xeroderma pigmentosum group G (XPG) and xeroderma pigmentosum group F (XPF) structure-specific endonucleases. Beyond nucleolysis, XPG and XPF regulate the overall efficiency of NER through various protein-protein interactions.
View Article and Find Full Text PDFHum Psychopharmacol
November 2023
Objective: To test the null hypothesis that oral intake of the dietary supplement carboxy alkyl ester (CAE) would have no effect on attention as revealed by mean rapid visual information processing (RVIP) scores.
Methods: In a randomized double-blind cross-over placebo-controlled trial, healthy participants (age 19-66 years) of both sexes were randomly assigned to consume 700 mg of CAE or 700 mg of placebo. They received baseline attention testing via the RVIP task.
J Cancer Surviv
February 2023
Purpose: Ototoxicity is considered a dose-limiting side effect of some chemotherapies. Hearing loss, in particular, can have significant implications for the quality of life for cancer survivors. Here, we review therapeutic approaches to mitigating ototoxicity related to chemotherapy.
View Article and Find Full Text PDFJ Toxicol Environ Health A
August 2022
A fundamental property of first-order sensory neurons is the ability to alter their response properties as a function of change in the statistical parameters of an input signal. Such neural adaptation shapes the performance features of contiguous neural circuits that ultimately drive sensory discrimination. The current study focused on whether combined exposure to jet fuel and noise might alter the capacity of the auditory nerve to adapt to stimulus presentation speed.
View Article and Find Full Text PDFCentral auditory nervous system dysfunction (CANSD) can manifest as hearing difficulty in the absence of audiometric abnormalities. Effects of noise or jet fuel exposure on the CANS are documented in animal models and humans. This study screened military personnel using the modified Amsterdam Inventory for Auditory Disability (mAIAD) to assess whether concurrent jet fuel and noise (JFN) exposures potentiate central auditory difficulties compared to noise only exposures.
View Article and Find Full Text PDFJ Toxicol Environ Health A
March 2022
Degenerate neural circuits exhibit "different" circuit properties yet produce similar circuit outcomes (many-to-one) which ensures circuit robustness and complexity. However, neuropathies may hijack degeneracy to yield robust and complex pathological circuits. The aim of the current study was to test the hypothesis that physiochemical exposure to combined jet fuel and noise might induce degeneracy in the brainstem.
View Article and Find Full Text PDFOver 1.1 billion individuals are at risk for noise induced hearing loss yet there is no accepted therapy. A long history of research has demonstrated that excessive noise exposure will kill outer hair cells (OHCs).
View Article and Find Full Text PDFAge-related and noise-induced hearing loss disorders are among the most common pathologies affecting Americans across their lifespans. Loss of auditory feedback due to hearing disorders is correlated with changes in voice and speech-motor control in humans. Although rodents are increasingly used to model human age- and noise-induced hearing loss, few studies have assessed vocal changes after acoustic trauma.
View Article and Find Full Text PDFNoise as a systemic stressor induces various organ dysfunctions and the underlying molecular pathology is unknown. Previous studies have shown that noise exposure results in the accumulation of DNA damage in auditory and non-auditory organs. The DNA damage response (DDR) is a global protective mechanism that plays a critical role in maintaining DNA integrity.
View Article and Find Full Text PDFJ Comp Physiol A Neuroethol Sens Neural Behav Physiol
August 2019
Acoustic communication is a fundamental component of mate and competitor recognition in a variety of taxa and requires animals to detect and differentiate among acoustic stimuli (Bradbury and Vehrencamp in Principles of animal communication, 2nd edn., Sinauer Associates, Sunderland, 2011). The matched filter hypothesis predicts a correspondence between peripheral auditory tuning of receivers and properties of species-specific acoustic signals, but few studies have assessed this relationship in rodents.
View Article and Find Full Text PDFIn response to DNA damage from ultraviolet (UV) radiation, bacteria deploy the SOS response in order to limit cell death. This bacterial SOS response is characterized by an increase in the recA gene that transactivates expression of multiple DNA repair genes. The current series of experiments demonstrate that a mammalian organ system (the cochlea) that is not evolutionarily conditioned to UV radiation can elicit SOS responses that are reminiscent of that of bacteria.
View Article and Find Full Text PDFJ Histochem Cytochem
March 2017
In response to toxic stressors, cancer cells defend themselves by mobilizing one or more epidermal growth factor receptor (EGFR) cascades that employ xeroderma pigmentosum-A (XPA) to repair damaged genes. Recent experiments discovered that neurons within the auditory nerve exhibit basal levels of EGFR+XPA co-expression. This finding implied that auditory neurons in particular or neurons in general have the capacity to mobilize an EGFR+XPA defense.
View Article and Find Full Text PDFAn understanding of the molecular pathology that underlies noise induced neurotoxicity is a prerequisite to the design of targeted therapies. The objective of the current experiment was to determine whether or not DNA damage is part of the pathophysiologic sequela of noise induced neurotoxicity. The experiment consisted of 41 hooded Long-Evans rats (2 month old males) that were randomized into control and noise exposed groups.
View Article and Find Full Text PDFOccupational exposure to complex blends of organic solvents is believed to alter brain functions among workers. However, work environments that contain organic solvents are also polluted with background noise which raises the issue of whether or not the noise contributed to brain alterations. The purpose of the current study was to determine whether or not repeated exposure to low intensity noise with and without exposure to a complex blend of organic solvents would alter brain activity.
View Article and Find Full Text PDFJ Am Acad Audiol
January 2016
Background: Permanent loss of outer hair cell (OHC) amplification may occur within days of acoustic overexposure. This loss of sensory function typically results in an immediate loss of neural sensitivity although neurodegeneration occurs months or years after damage to OHCs. This delay in neurodegeneration might provide an opportunity to preserve neural sensitivity although OHC amplification is permanently lost.
View Article and Find Full Text PDFXeroderma pigmentosum-A (XPA) is a C4-type zinc-finger scaffolding protein that regulates the removal of bulky-helix distorting DNA damage products from the genome. Phosphorylation of serine residues within the XPA protein is associated with improved protection of genomic DNA and cell death resistance. Therefore, kinase signaling is one important mechanism for regulating the protective function of XPA.
View Article and Find Full Text PDFJ Toxicol Environ Health A
January 2016
More than 800 million L/d of hydrocarbon fuels is used to power cars, boats, and jet airplanes. The weekly consumption of these fuels necessarily puts the public at risk for repeated inhalation exposure. Recent studies showed that exposure to hydrocarbon jet fuel produces lethality in presynaptic sensory cells, leading to hearing loss, especially in the presence of noise.
View Article and Find Full Text PDFPurpose. Tinnitus and sleep disturbance are prevalent in veterans, and a better understanding of their relationship can help with tinnitus treatment. Materials and Methods.
View Article and Find Full Text PDFJ Toxicol Environ Health A
April 2014
Jet propulsion fuel-8 (JP-8) is a kerosene-based fuel that is used in military jets. The U.S.
View Article and Find Full Text PDFObjective: Human genetic mutations that affect the N-terminal head-domain of the nonmuscle myosin-II (MyoII) molecule can result in nonsyndromic sensorineural hearing loss but the underlying mechanism is unknown. Ultimately, MyoII must be appropriately localized in order to execute endogenous functions. The aim of the current study is to determine whether the head-domain of MyoII regulates in vivo localization of the molecule in living and fixed preparations of the auditory organ.
View Article and Find Full Text PDFNucleotide excision repair (NER) is a defensive mechanism that limits genomic stress through genetically distinct cascades that employs Cockayne syndrome-A (CSA), the xeroderma pigmentosum-C (XPC) and the xeroderma pigmentosum-A (XPA) proteins. Noise exposure induces stress within the spiral ganglia. Therefore, it was posited that noise exposure would mobilize NER proteins within spiral ganglion neurons.
View Article and Find Full Text PDFABSTRACT In response to stress, spiral ganglion neurons may remodel intracellular pools of DNA repair proteins. This hypothesis was addressed by determining the intracellular location of three classic DNA excision repair proteins (XPA, CSA, and XPC) within the neurons under normal conditions, one day after noise stress (105 dB/4 hr) and following DNA repair adjuvant therapy with carboxy alkyl esters (CAEs; 160 mg/kg/28 days). Under normal conditions, three intracellular compartments were enriched with at least one repair protein.
View Article and Find Full Text PDFThis study tested the hypothesis that hydrophilic chemotypes of the medicinal vine Uncaria tomentosa (UT) would facilitate recovery of sensorineural functions following exposure to a damaging level of noise. The particular chemotypes investigated were carboxy alkyl esters (CAE) which are known to exhibit multifunctional cytoprotective properties that include: enhanced cellular DNA repair, antioxidation and anti-inflammation. Long-Evans rats were divided into four treatment groups: vehicle-control, noise-only, CAE-only and CAE+noise.
View Article and Find Full Text PDFObjective: Human mutations in the DNA repair genes, Xeroderma pigmentosum (XP)-C and XPA result in hearing loss, which has fueled the hypothesis that there is a significant demand for these genes in protecting cochlear genetic material. Therefore, we quantified the level of XPC and XPA mRNA in the mammalian cochlea.
Design: XPC and XPA mRNAs were purified from the cochlea of 15 Fischer344 rats and quantified using SYBR Green chemistry.