Clomipramine counteracts lipid raft disturbance due to short-term muscle disuse. (18th January 2018)

• Record Type: Journal Article
• Authors: Bryndina, Irina G.; Shalagina, Maria N.; Sekunov, Alexey V.; Zefirov, Andrei L.; Petrov, Alexey M.
• Is Part Of: Neuroscience letters. Volume 664(2018)
• Page Start: 1
• Page End: 6
• Publication Date: 2018-01-18
• Subjects: aSMase acid sphingomyelinase -- HS hindlimb suspension -- CTxB subunit B from cholera toxin -- αBtx α-bungarotoxin -- nAChRs nicotinic acetylcholine receptors; Skeletal muscle -- Hindlimb suspension -- Lipid rafts -- Acid sphingomyelinase -- Ceramide -- Clomipramine; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2017.11.009
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Hindlimb suspension (HS) for 12 h changes membrane properties in soleus muscle. We try to prevent 12 h of HS-induced raft disturbance by clomipramine pretreatment. Clomipramine prevents ceramide accumulation and cholesterol loss after 12 h of HS. Clomipramine counteracts loss of raft integrity in junctional region after 12 h of HS. Abstract: Disuse-induced skeletal muscle dysfunction is a serious consequence of long-term spaceflight, numerous diseases and conditions for which treatment possibilities are still strictly limited. We have previously shown that acute hindlimb suspension (HS)-mediated disuse disrupts membrane lipid rafts in the unloaded muscle. Here, we investigated whether pretreatment of rats with the inhibitor of acid sphingomyelinase, clomipramine (1.25 mg/g/day, intramuscularly, for 5 days before HS), is able to hinder the loss in lipid raft integrity in response to 12 h of HS. Clomipramine pretreatment significantly counteracted the decrease in labeling of the plasma membranes with lipid raft markers (fluorescent cholera toxin B subunit and bodipy-GM1-ganglioside) specifically in the junctional regions of the suspended soleus muscle. This was associated with: a) enhancing raft disrupting potential of exogenous sphingomyelinase in the junctional membranes; b) prevention of both ceramide accumulation and cholesterol loss; c) prevention of decline in nicotinic acetylcholine receptor labeling in the unloaded muscle. Our data suggest that sphingomyelinase-mediated raft disturbance serves as one of the earlier events in HS effects.