A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00511368" target="_blank" >RIV/61388963:_____/19:00511368 - isvavai.cz</a>

Výsledek na webu

<a href="https://journals.lww.com/pain/Abstract/2019/12000/A_potential_role_for_T_type_calcium_channels_in.13.aspx" target="_blank" >https://journals.lww.com/pain/Abstract/2019/12000/A_potential_role_for_T_type_calcium_channels_in.13.aspx</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1097/j.pain.0000000000001669" target="_blank" >10.1097/j.pain.0000000000001669</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy

Popis výsledku v původním jazyce

Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, our in vitro studies indicate that homocysteine enhances recombinant T-type calcium currents by promoting the recycling of Cav3.2 channels back to the plasma membrane through a protein kinase C-dependent signaling pathway that requires the direct phosphorylation of Cav3.2 at specific loci. Altogether, these results reveal an unrecognized signaling pathway that modulates the expression of T-type calcium channels, and may potentially contribute to the development of peripheral neuropathy associated with homocysteinemia.

Název v anglickém jazyce

A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy

Popis výsledku anglicky

Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, our in vitro studies indicate that homocysteine enhances recombinant T-type calcium currents by promoting the recycling of Cav3.2 channels back to the plasma membrane through a protein kinase C-dependent signaling pathway that requires the direct phosphorylation of Cav3.2 at specific loci. Altogether, these results reveal an unrecognized signaling pathway that modulates the expression of T-type calcium channels, and may potentially contribute to the development of peripheral neuropathy associated with homocysteinemia.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pain

ISSN

0304-3959

e-ISSN

—

Svazek periodika

160

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

2798-2810

Kód UT WoS článku

000512908700013

EID výsledku v databázi Scopus

2-s2.0-85074965976