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Prestin forms tetramer with each subunit being mechanically independent

Journal of Otology 2009年第2期4卷 86-97页

作者： WANG Xiang 1, GUO Wei-wei 2, HE David Zhi-Zhou1, YANG Shi-Ming 2 1 Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA 2 Institute of Otolaryngology, Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853 Department of Biomedical Sciences Creighton University School of Medicine Omaha NE 68178 USA Institute of Otolaryngology Department of Otolaryngology Head and Neck Surgery Chinese PLA General Hospital Beijing 100853

Prestin is the motor protein of cochlear outer hair cells （OHCs）. It is able to perform rapid and reciprocal electromechanical conversion that underlies OHC electromotility. Due to the inadequate size of a single prestin molecule to form the2 nm intramembraneous protein particles （IMPs） in the OHC lateral membrane （LM）, the possibility of prestin oligomerization has been proposed. It has been suggested that prestin molecules form highorder oligomers, most likely as the tetramer, in heterologous systems. In OHCs, however, the oligomeric structure of prestin remains unclear. Here we calculated the prestin-related charge density in both gerbil and guinea pig OHCs through measuring their nonlinear capacitance （NLC） and LM surface area, showing that the average charge density （22, 608 μm-2 in gerbils; 19, 460 μm-2 in guinea pigs） is statistically 4 times the average density of IMPs （5,686 μm-2 in gerbils; 5, 000 μm-2 in guinea pigs）. This suggests that each IMP contains four prestin molecules based upon the notion that each prestin transfers a single elementary charge, implying that prestin forms tetramers in OHCs. To determine whether the prestin tetramer functions as a mechanical unit, we subsequently compared the slope factors （α） of electromotility and NLC simultaneously measured from the same OHC, showing that the α values of the two are statistically the same. This suggests that each prestin molecule in the tetramer is mechanically independent and equally contributes to OHC electromotility.

关键词： Prestin oligomer outer hair cells electromotility nonlinear capacitance gerbil

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Contribution of animal models to the research of the causes of diabetes

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World Journal of Diabetes 2010年第5期1卷 137-140页

作者： Eleazar Shafrir Hadassah University Hospital and Hebrew University-Hadassah Medical School

In most publications,animal models of diabetes have mainly been investigated for their multiple etiologies as well as for changes leading to diabetes and their genetic *** which seem important and need a special research endeavor are the mechanism of the causes of diabetes and the lapse into complications in different species,their molecular basis and possible arrest and prevention.A concise list and and short discussion of the intensively studied rodents is present ed of spontaneous or nutritional background causing Type 2 diabetes but omitting diabetes evoked by transg enic manipulations or gene knockout techniques.

关键词： Animal model Mouse Rat Psammomys gerbil Diabetes

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Experimental study of transient cochlear ischemia as a cause of sudden deafness

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World Journal of Otorhinolaryngology 2013年第1期3卷 1-15页

作者： Kiyofumi Gyo Department of Otorhinolaryngology Head and Neck Surgery Ehime University Shizukawa

The etiology of sudden deafness or idiopathic sudden sensorineural hearing loss(ISSHL) remains unclear. Over the past 15 years, we have investigated the mechanisms of ischemic-induced hearing loss using a gerbil model of transient cochlear ischemia. In the gerbil, cochlear ischemia can be induced by occluding the bilateral vertebral arteries simultaneously at the neck, because the posterior communicating arteries of the Circle of Willis close spontaneously around 1 mo after birth. When 15 min ischemia was loaded on this animal, permanent hearing loss of about 25 d B and the death of hair cells, especially inner hair cells were induced. These pathological changes were mainly due to lack of an energy source, glutamate excitotoxicity, and the production of free radicals, especially superoxide and nitrous oxide species. Ischemic damage could be prevented by various procedures, such as cooling the cochlea, intratympanic administration of insulin-like growth factor 1 or AM-111(an anti-apoptotic agent), and systemic administration of prednisolone(steroid), edarabone(free radical scavenger), ginsenoside Rb1(Kanpo), hematopoietic stem cells, glia-cell derived neurotrophic factor, and liposome-encapsulated hemoglobin(artificial red blood cells). We also found that the cochlea was protected by the ischemic tolerance, indi-cating that minor cochlear ischemia alleviates or prevents inner ear damage in subsequent severe cochlear ischemia. As ISSHL usually occurs suddenly, with no preceding sign or symptom, we suggest that most ISSHL cases are caused by circulatory disturbance, probably at the stria vascularis.

关键词： Sudden deafness Occlusion of vertebral artery Mongolian gerbil Loss of inner hair cell Ischemic tolerance Cochlear hypothermia

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