Guthrie O'neil W
Cell & Molecular Pathology Laboratory, Department of Communication Sciences and Disorders, Northern Arizona University, Flagstaff, Arizona (OWG).
Research Service-151, Loma Linda Veterans Affairs Medical Center, Loma Linda, California (OWG).
J Histochem Cytochem. 2017 Mar;65(3):173-184. doi: 10.1369/0022155416683661. Epub 2017 Jan 5.
In response to toxic stressors, cancer cells defend themselves by mobilizing one or more epidermal growth factor receptor (EGFR) cascades that employ xeroderma pigmentosum-A (XPA) to repair damaged genes. Recent experiments discovered that neurons within the auditory nerve exhibit basal levels of EGFR+XPA co-expression. This finding implied that auditory neurons in particular or neurons in general have the capacity to mobilize an EGFR+XPA defense. Therefore, the current study tested the hypothesis that noise stress would alter the expression pattern of EGFR/XPA within the auditory nerve. Design-based stereology was used to quantify the proportion of neurons that expressed EGFR, XPA, and EGFR+XPA with and without noise stress. The results revealed an intricate neuronal response that is suggestive of alterations to both co-expression and individual expression of EGFR and XPA. In both the apical and middle cochlear coils, the noise stress depleted EGFR+XPA expression. Furthermore, there was a reduction in the proportion of neurons that expressed XPA-alone in the middle coils. However, the noise stress caused a significant increase in the proportion of neurons that expressed EGFR-alone in the middle coils. The basal cochlear coils failed to mobilize a significant response to the noise stress. These results suggest that EGFR and XPA might be part of the molecular defense repertoire of the auditory nerve.
针对毒性应激源,癌细胞通过动员一种或多种利用着色性干皮病A(XPA)来修复受损基因的表皮生长因子受体(EGFR)级联反应进行自我保护。最近的实验发现,听神经内的神经元呈现出EGFR与XPA共表达的基础水平。这一发现意味着,尤其是听神经元或一般的神经元有能力动员EGFR+XPA防御机制。因此,本研究检验了噪声应激会改变听神经内EGFR/XPA表达模式的假设。采用基于设计的体视学方法来量化有无噪声应激情况下表达EGFR、XPA以及EGFR+XPA的神经元比例。结果揭示了一种复杂的神经元反应,提示EGFR和XPA的共表达及各自的表达均发生了改变。在耳蜗顶部和中部蜗管,噪声应激使EGFR+XPA表达减少。此外,中部蜗管中单独表达XPA的神经元比例降低。然而,噪声应激使中部蜗管中单独表达EGFR的神经元比例显著增加。耳蜗基部蜗管对噪声应激未产生显著反应。这些结果表明,EGFR和XPA可能是听神经分子防御机制的一部分。