Acid-sensing ion channel 2 (asic 2) and trkb interrelationships within the intervertebral disc.
نویسندگان
چکیده
The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. They express acid-sensing ion channels (ASICs), gated by extracellular protons and mechanical forces, as well as neurotrophins and their signalling receptors. In the nervous tissues some neurotrophins regulate the expression of ASICs. The expression of ASIC2 and TrkB in human normal and degenerated IVD was assessed using quantitative-PCR, Western blot, and immunohistochemistry. Moreover, we investigated immunohistochemically the expression of ASIC2 in the IVD of TrkB-deficient mice. ASIC2 and TrkB mRNAs were found in normal human IVD and both increased significantly in degenerated IVD. ASIC2 and TrkB proteins were also found co-localized in a variable percentage of cells, being significantly higher in degenerated IVD than in controls. The murine IVD displayed ASIC2 immunoreactivity which was absent in the IVD of TrkB-deficient mice. Present results demonstrate the occurrence of ASIC2 and TrkB in the human IVD, and the increased expression of both in pathological IVD suggest their involvement in IVD degeneration. These data also suggest that TrkB-ligands might be involved in the regulation of ASIC2 expression, and therefore in mechanisms by which the IVD cells accommodate to low pH and hypertonicity.
منابع مشابه
Acid-sensing ion channel 1a regulates the survival of nucleus pulposus cells in the acidic environment of degenerated intervertebral discs
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متن کاملNonstandard abbreviations: GABA: γ-aminobutyric acid TM: transmembrane domain Amil: amiloride ASIC: acid-sensing ion channel GMQ: 2-guanidine-4-methylquinazoline EGTA: ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid HEPES: 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid TEA-Cl: tetraethylammonium chloride DMSO: dimethylsulfoxide GLIC: Gloeobacter violaceus pentameric ligand-gated ion channel PAM: positive allosteric modulation
Amil: amiloride ASIC: acid-sensing ion channel GMQ: 2-guanidine-4-methylquinazoline EGTA: ethylene
متن کاملAcid-sensing ion channel 1a regulates the survival of nucleus pulposus cells in the acidic environment of degenerated intervertebral discs
OBJECTIVES Activation of acid-sensing ion channel 1a (ASIC1a) is responsible for tissue injury caused by acidosis in nervous systems. But its physiological and pathological roles in nucleus pulposus cells (NPCs) are unclear. The aim of this study is to investigate whether ASIC1a regulates the survival of NPCs in the acidic environment of degenerated discs. MATERIALS AND METHODS NPCs were isol...
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ورودعنوان ژورنال:
- International journal of clinical and experimental pathology
دوره 8 9 شماره
صفحات -
تاریخ انتشار 2015