A putative role of p53 pathway against impulse noise induced damage as demonstrated by protection with pifithrin-alpha and a Src inhibitor.

Exposure to high-level noise leads to oxidative stress and triggers apoptosis of the hair cells. This study examined whether p53, a tumor suppressor protein, is activated in the cochlea following impulse noise exposure. Inhibition of p53 with pifithrin alpha, a specific p53 inhibitor, or KX1-004, a Src-protein tyrosine kinase inhibitor, was tested to determine if p53 inhibition could reduce noise-induced hearing loss and cochlear damage.

Regulation of PSA secretion and survival signaling by calcium-independent phopholipase A(2)beta in prostate cancer cells.

Background: Serum prostate specific antigen (PSA) levels in prostate cancer patients serve as a useful biomarker for diagnosing and monitoring prostate cancer. Recently, secreted PSA has been characterized as an autocrine survival factor through activation of Akt and induction of AR. In the normal prostate, PSA is secreted in the lumen of prostatic ducts to lyse proteins in the seminal coagulum.

Linear quantitation of Abeta aggregation using Thioflavin T: reduction in fibril formation by colostrinin.

Thioflavin T (ThT) fluorescence is a commonly used method to monitor Abeta protein fibril formation. This method is particularly attractive since ThT fluoresces only when bound to fibrils, the reaction is completed within 1min and ThT does not interfere with aggregation of Abeta fibrils. One of the drawbacks of this method is the lack of a strict quantitative relationship between ThT fluorescence and fibril content.

RETRACTED: Prevention of hearing loss from noise exposure using Src inhibitors.

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Extremely rapid induction of outer hair cell apoptosis in the chinchilla cochlea following exposure to impulse noise.

We have reported the presence of OHC apoptosis and necrosis in the organ of Corti following exposure to intense noise. The current study was designed to investigate the rapidity and the initial pattern of outer hair cell (OHC) death induced by exposure to impulse noise. Chinchillas were exposed to 75 pairs of impulse noise at 155 dB peak sound pressure level presented over a time period of 75 s.

Protective effect of colostrinin on neuroblastoma cell survival is due to reduced aggregation of beta-amyloid.

Colostrinin (CLN), a mixture of proline-rich polypeptides, has shown a stabilizing effect on cognitive function in Alzheimer's patients measured by the Alzheimer's disease Assessment Scale-cognitive (ADAS-cog) and in Instrumental Activities of Daily Living (ILDL) in recently conducted clinical trials. The aim of this study was to elucidate a possible mode of action of CLN in the treatment of Alzheimer's disease. Here, we report that CLN prevents the aggregation of beta-amyloid peptide Abeta (1-40) in vitro.

Paraquat-induced hair cell damage and protection with the superoxide dismutase mimetic m40403.

Some forms of ototoxicity appear to be mediated primarily by the superoxide radical; however, the exact role the superoxide radical plays in cochlear damage is not well understood because most ototoxic drugs produce multiple reactive oxygen species. To characterize the role of the superoxide radical in cochlear damage and the protective effect of compounds that inactivate superoxide, we treated mouse cochlear organotypic cultures for 24 h with paraquat, an herbicide that produces high levels of superoxide. M40403, a highly specific, nonpeptidyl mimetic of superoxide dismutase, was added to some cultures to inactivate the superoxide radical generated by paraquat.

Quantitative analysis of apoptotic and necrotic outer hair cells after exposure to different levels of continuous noise.

We have reported that by 2 days after noise exposure the size of cochlear lesion was expanding by outer hair cells (OHCs) dying either by apoptosis or necrosis. The current study was designed to compare the prevalence of the two cell death pathways as a function of time after exposure to noises of different levels. Chinchillas were exposed to a narrow band noise at either 104 or 108 dB SPL for 1 h.

The caspase pathway in noise-induced apoptosis of the chinchilla cochlea.

We previously reported that intense noise exposure causes outer hair cell (OHC) death primarily through apoptosis. Here we investigated the intracellular signal pathways associated with apoptotic OHC death. Chinchillas were exposed to a 4 kHz narrowband noise at 110 dB SPL for 1 h.

Noise-induced hearing loss in chinchillas pre-treated with glutathione monoethylester and R-PIA.

The protective effects of glutathione monoethylester (GEE) and GEE in combination with R-N6-phenylisopropyladenosine (R-PIA) were evaluated in the chinchilla when exposed to impulse (145 dB pSPL) or continuous (105 dB SPL, 4 kHz OB) noise. Six groups of 10 chinchillas were used as subjects. Before exposure to noise, the subjects were anesthetized, a 30 microl drop of drug was placed on the round window (GEE [50, 100, 150 mM], GEE 50 mM and R-PIA).

F-actin cleavage in apoptotic outer hair cells in chinchilla cochleas exposed to intense noise.

Apoptosis is an active cell death pathway involved in a variety of pathological conditions, including noise-induced outer hair cell (OHC) death. During this process, the cytoskeletal proteins have been found to be either damaged and/or enzymatically disassembled in several cell types, leading to formation of apoptotic manifestations. This study was designed to examine the cleavage of filamentous actin (F-actin), an important cytoskeletal protein, in the cochlear OHCs after noise exposure.

Involvement of apoptosis in progression of cochlear lesion following exposure to intense noise.

It has been known for some time that noise-induced outer hair cell (OHC) death in the cochlea continues well after the termination of a noise exposure. However, the underlying mechanisms leading to the expansion of a cochlear lesion are not fully understood. Here we report involvement of the apoptotic pathway in the progression of OHC death in the chinchilla cochlea following exposure to a 4 kHz narrow band noise at 110 dB SPL for 1 h.