Protein profile of mouse endolymph suggests a role in controlling cochlear homeostasis
Masatoshi Fukuda,
Hiroki Okanishi,
Daisuke Ino,
Kazuya Ono,
Takeru Ota,
Eri Wakai,
Takashi Sato,
Yumi Ohta,
Yoshiaki Kikkawa,
Hidenori Inohara,
Yoshikatsu Kanai,
Hiroshi Hibino
Affiliations
Masatoshi Fukuda
Division of Glocal Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Otorhinolaryngology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Hiroki Okanishi
Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Daisuke Ino
Division of Glocal Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Kazuya Ono
Division of Glocal Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Takeru Ota
Division of Glocal Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Eri Wakai
Division of Glocal Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Takashi Sato
Department of Otorhinolaryngology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Yumi Ohta
Department of Otorhinolaryngology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Yoshiaki Kikkawa
Deafness Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan; Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; AMED-CREST, AMED, Osaka 565-0871, Japan
Hidenori Inohara
Department of Otorhinolaryngology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Yoshikatsu Kanai
Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Institute for Open and Transdisciplinary Research Initiatives, Osaka 565-0871, Japan; Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka 565-0871, Japan
Hiroshi Hibino
Division of Glocal Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; AMED-CREST, AMED, Osaka 565-0871, Japan; Corresponding author
Summary: The cochlea contains two extracellular fluids, perilymph and endolymph. Endolymph exhibits high potential of approximately +80 to +110 mV (depending on species), which sensitizes sensory hair cells. Other properties of this unique fluid remain elusive, owing to its minuscule volume in rodent cochlea. We therefore developed a technique to collect high-purity endolymph from mouse cochleae. Comprehensive proteomic analysis of sampled endolymph using liquid chromatography with mass spectrometry identified 301 proteins, dominated by molecules engaged in immunity and proteostasis. Approximately 30% of these proteins were undetectable in our perilymph. A combination of mass spectrometry and different approaches revealed that, compared to perilymph, endolymph was enriched with α2-macroglobulin, osteopontin, apolipoprotein D, apolipoprotein E, and apolipoprotein J/clusterin. In other cells or tissues, α2-macroglobulin, apolipoprotein E, and apolipoprotein J contribute to the clearance of degraded proteins from extracellular fluid. Altogether, with the proteins described here, endolymph may play a protective role in stabilizing cochlear homeostasis.
