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Up-regulation of Ca2+/CaMKII/CREB signaling in salicylate-induced tinnitus in rats

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Abstract

The purpose of the study was to investigate the changes of Ca2+/calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer. Expressions of calmodulin (CaM), N-methyl-d-aspartate receptor 2B subunit (NR2B), calcium-calmodulin kinase II (CaMKII), and cAMP response element-binding protein (CREB) were detected with Western blot. Tinnitus model was successfully established by the intraperitoneal administration of salicylate in rats. Compared with rats in NC and NS groups, salicylate administration significantly elevated CaM, NR2B, phospho-CaMKII and phospho-CREB expression in auditory cortex from tinnitus model group (p < 0.05), and the free intracellular Ca2+ concentrations (p < 0.05). Our data reveal that salicylate administration causes tinnitus symptoms and elevates Ca2+/CaMKII/CREB signaling pathway in auditory cortex cells. Our study likely provides a new understanding of the development of tinnitus.

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Authors and Affiliations

  1. Department of Neurology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, 110001, China

    Jiuhan Zhao, Xiaohong Wang & Xiuli Shang

  2. Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, 110001, China

    Biao Wang

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  1. Jiuhan Zhao
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  2. Biao Wang
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  4. Xiuli Shang
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Correspondence to Xiuli Shang.

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Zhao, J., Wang, B., Wang, X. et al. Up-regulation of Ca2+/CaMKII/CREB signaling in salicylate-induced tinnitus in rats. Mol Cell Biochem 448, 71–76 (2018). https://doi.org/10.1007/s11010-018-3314-z

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  • DOI: https://doi.org/10.1007/s11010-018-3314-z

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