Differential expression of unconventional myosins in apoptotic and regenerating chick hair cells confirms two regeneration mechanisms
Differential expression of unconventional myosins in apoptotic and regenerating chick hair cells confirms two regeneration mechanisms
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DOI：
10.1002/cne.21114
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发表时间：
2006-12-10
影响因子：
2.5
通讯作者：
Cotanche, Douglas A.
中科院分区：
文献类型：
--
作者：
Duncan, Luke J.;Mangiardi, Dominic A.;Cotanche, Douglas A.
强烈的噪音、衰老和氨基糖苷类抗生素会损害内耳的毛细胞。庆大霉素对毛细胞造成氧化损伤，诱导细胞凋亡。在哺乳动物中，毛细胞丢失会导致永久性的听力和平衡障碍。相比之下，鸟类可以再生丢失的毛细胞来恢复听觉和前庭功能。这项研究检测了毛细胞死亡和再生过程中肌球蛋白VI和肌球蛋白VIIa的变化，这两种非常规肌球蛋白对正常毛细胞的形成和功能至关重要。在细胞凋亡的后期，受损的毛细胞从感觉上皮中排出。这两种肌球蛋白的标记强度增加了4-5倍，肌球蛋白VI重新分布到立体纤毛束中，同时伴随着射血。在毛细胞再生过程中观察到两种不同的机制。增殖支持细胞在庆大霉素处理后60小时开始DNA合成，在庆大霉素处理后72小时达到高峰。其中一些有丝分裂产生的细胞在庆大霉素后108小时(溴脱氧尿苷(BrdU)注射36小时后)开始分化为毛细胞，肌球蛋白VI和BrdU的标记证明了这一点。肌球蛋白VIIa在庆大霉素作用120小时后才在新生毛细胞中表达。此外，一群支持细胞在庆大霉素治疗后78小时表达肌球蛋白VI，在90小时表达肌球蛋白VIIa。这些细胞没有BrdU标记，而且分化得太早，不可能是有丝分裂的起源，这表明它们是由支持细胞直接转分化成毛细胞而产生的。
Hair cells of the inner ear are damaged by intense noise, aging, and aminoglycoside antibiotics. Gentamicin causes oxidative damage to hair cells, inducing apoptosis. In mammals, hair cell loss results in a permanent deficit in hearing and balance. In contrast, avians can regenerate lost hair cells to restore auditory and vestibular function. This study examined the changes of myosin VI and myosin VIIa, two unconventional myosins that are critical for normal hair cell formation and function, during hair cell death and regeneration. During the late stages of apoptosis, damaged hair cells are ejected from the sensory epithelium. There was a 4-5-fold increase in the labeling intensity of both myosins and a redistribution of myosin VI into the stereocilia bundle, concurrent with ejection. Two separate mechanisms were observed during hair cell regeneration. Proliferating supporting cells began DNA synthesis 60 hours after gentamicin treatment and peaked at 72 hours postgentamicin treatment. Some of these mitotically produced cells began to differentiate into hair cells at 108 hours after gentamicin (36 hours after bromodeoxyuridine (BrdU) administration), as demonstrated by the colabeling of myosin VI and BrdU. Myosin VIIa was not expressed in the new hair cells until 120 hours after gentamicin. Moreover, a population of supporting cells expressed myosin VI at 78 hours after gentamicin treatment and myosin VIIa at 90 hours. These cells did not label for BrdU and differentiated far too early to be of mitotic origin, suggesting they arose by direct transdifferentiation of supporting cells into hair cells.