Abstract
A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Therefore, in this study, we aimed to investigate the role of PIN1 in protecting hair cells and auditory HEI-OC1 cells from senescence. Enzyme-linked immunosorbent assays, immunohistochemistry, and immunofluorescence were used to detect the PIN1 protein level in the serum of ARHL patients and C57BL/6 mice in different groups, and in the SGCs and HCs of young and aged C57BL/6 mice. In addition, a model of HEI-OC1 cell senescence induced by H2O2 was used. Adult C57BL/6 mice were treated with juglone, or juglone and NAC, for 4 weeks. Interestingly, we found that the PIN1 protein expression decreased in the serum of patients with ARHL, in senescent HEI-OC1 cells, and in the cochlea of aged mice. Moreover, under H2O2 and juglone treatment, a large amount of ROS was produced, and phosphorylation of p53 was induced. Importantly, PIN1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α. Overexpression of PIN1 reversed the increased level of p-p53 and rescued HEI-OC1 cells from senescence. Furthermore, PIN1 mediated cellular senescence by the PI3K/Akt/mTOR signaling pathway. In vivo data from C57BL/6 mice showed that treatment with juglone led to hearing loss. Taken together, these findings demonstrated that PIN1 may act as a vital modulator in hair cell and HEI-OC1 cell senescence.
Highlights
Age-related hearing loss (ARHL) or presbycusis is a prevalent disease in aging people [1, 2]
The results showed that senescence-associated βgalactosidase- (SA-β-gal-) positive cells in the aged mice were more abundant than those in the young mice in spiral ganglion cells (SGCs) (Figure 2(b)) and hair cells (HCs) (Figure 2(c))
To further study whether the reduction in PIN1 expression could induce hair cell senescence, we treated the mice with juglone, or juglone and NAC at the same time
Summary
Age-related hearing loss (ARHL) or presbycusis is a prevalent disease in aging people [1, 2]. Hearing loss occurs in most people as they age. With the aging of the population worldwide, more than 500 million people suffer ARHL [3]. This condition significantly affects the daily communication of older people, and has been shown to be associated with predisposing cognitive impairment and dementia. ARHL is characterized by an age-dependent decline in auditory function. This condition is primarily due to the loss of hair cells and spiral ganglion cells (SGCs) in the cochlea [4].
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