Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis was induced in the cochlea by the injection of keyhole limpet hemocyanin (KLH) into the endolymphatic sac of guinea pigs and immunohistochemically examined. Keyhole limpet hemocyanin was injected into the right endolymphatic sac. The temporal bones were fixed via cardiac infusion of fixative and immunohistochemically stained for caspase-activated deoxyribonuclease or caspase 3. Endolymphatic hydrops became evident in the cochlea 1 day after the injection of keyhole limpet hemocyanin (n=6). The temporal bones in the control group did not show any caspase-activated deoxyribonuclease or caspase 3 immunoreactivity (n=6). Immunoreactivity for caspase 3 was detected in the supporting cells of the organ of Corti, the stria vascularis and the spiral ganglion cells. Caspase-activated deoxyribonuclease was also detected in the same areas. These findings suggest that apoptosis is involved in the pathogenesis of endolymphatic hydrops. This phenomenon could lead to cochlear dysfunction, as seen in endolymphatic hydrops.
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PMID:Expression of caspase-activated deoxyribonuclease (CAD) and caspase 3 (CPP32) in the hydropic cochlea of guinea pigs - second report. 1210 29

The aim of this study was to investigate the involvement of oxidative stress and apoptosis in an animal model of Meniere's disease. Endolymphatic hydrops (ELH) is generally accepted as the decisive histological characteristic of Meniere's disease. Closure of the endolymphatic duct (Kimura's method) was used to induce endolymphatic hydrops in guinea pigs. Sham-operated animals served as controls. After 4 weeks the animals operated showed a significant elevation of the hearing thresholds as measured by audiometric brainstem responses (ABR) pre- and postoperatively. Immediately after the second ABR measurement, the animals were sacrificed for further immunohistological examinations of the inner ear with specific antibodies to active caspase-3 (cas-3) as a marker for apoptosis and antibodies to 8-isoprostane (8-iso) and nitrotyrosine (NT) as indicators of oxidative stress. Compared with the sham-operated controls, hydropic cochleae showed strong immunostaining for both oxidative stress markers in spiral ganglion cells, in the blood-vessels and fibrocytes of the lateral wall, as well as in supporting cells of the organ of Corti. Activation of cas-3 in spiral ganglion cells and the lateral wall was found exclusively in hydropic cochleae. Our findings suggest that oxidative stress is involved in the development of endolymphatic hydrops and may lead to cellular damage which induces apoptosis by activation of cas-3. Apoptotic cell death might contribute to the sensorineural hearing loss found in later stages of Meniere's disease.
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PMID:Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea. 1581 95

The aim of this study was to investigate the protective effects of vincamine in endolymphatic hydrops (ELH). After ELH guinea pigs treated by vincamine, the concentration of VAP in plasma, and the levels of cAMP, MDA, SOD, GSH-Px in right cochlea were measured using spectrophotometric method. The V2R, NMDAR1, p-NMDAR1, AQP2, p-AQP2, caspase3/9 and c-caspase3/9 expressions in right cochlea were detected using western blot analysis. The cochlear hydrops degree and SGNs density were evaluated by hemotoxylin and eosin staining (HE) test. Normal hearing and vestibular function were warranted by the tests of auditory brainstem response (ABR) and electronystagmography (ENG). After glutamate-injured SGNs treated with vincamine, the MDA, SOD GSH-Px, NGF, BDNF, NT3, NT4 and Trks levels were measured. Meanwhile, the Bcl2, Bax, NMDAR1, p-NMDAR1, PI3K, p-PI3K, Akt, p-Akt, caspase3/9 and cleaved-caspase3/9 expression levels were detected. Furthermore, the viability, apoptosis and necrosis of SGNs were tested by MTT and Hoechst/PI staining methods. The results indicated that vincamine could significantly inhibit the expression levels of cAMP, MDA, V2R, p-NMDAR1, p-AQP2 and c-caspase-3/-9 in cochlea, alleviate the cochlear hydrops degree, regulate the audiological and vestibular dysfunctions. The SGNs density, SOD and GSH-Px levels were also increased by vincamine. In vincamine-treating groups, the MDA, Bax, p-NMDAR1, and c-caspase3/9 levels were observably decreased, while SGNs survival, SOD, GSH, NGF, BDNF, NT3, NT4, Trks, Bcl2, p-PI3K, p-Akt expressions were improved. The present study indicated a novel use of vincamine in suppressing ELH formation by down-regulating the VAP/AQP2 signaling pathway. It also manifested that vincamine exerted protective effects on hearing via improving neurotrophin-dependent PI3K/Akt signaling pathway in SGNs.
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PMID:Vincamine exerts protective effect on spiral ganglion neurons in endolymphatic hydrops guinea pig models. 3066 16