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Heart failure increases neutral sphingomyelinase activity and ceramide content in rat diaphragm
Author(s) -
Ferreira Leonardo,
Deevska Gergana M.,
Nikolova-Karakashian Mariana,
Yoo Jeung-ki,
Christou Demetra D.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1075.13
Subject(s) - ceramide , sphingomyelin , medicine , skeletal muscle , endocrinology , acid sphingomyelinase , sphingolipid , heart failure , sphingomyelin phosphodiesterase , sphingosine , diaphragm (acoustics) , chemistry , cardiology , biochemistry , cholesterol , apoptosis , physics , receptor , acoustics , loudspeaker
Patients with chronic heart failure (CHF) have skeletal muscle weakness and elevated secretory sphingomyelinase activity. Sphingomyelinase (SMase) acts through ceramide to depress skeletal muscle force in vitro . We hypothesized that diaphragm weakness in CHF is accompanied by increases in SMase activity and tissue ceramide content. We studied rats 14–16 weeks after myocardial infarction (n = 5–10) and sham surgery (n = 10–13). CHF was confirmed by a decrease in left‐ventricular fractional shortening measured by echocardiography (Sham 38 ± 2%, CHF 28 ± 1%; P < 0.05). Skeletal muscle dysfunction in CHF was confirmed by decreased maximal tetanic force of diaphragm strips (in N/cm 2 : Sham 30 ± 0.6, CHF 26 ± 0.5; P < 0.05). CHF elicited a 27% increase ( P < 0.05) in neutral SMase (N‐SMase) activity. Consistent with this finding, total ceramide content was elevated in CHF diaphragm (in pmol/mg protein: Sham, 280 ± 5 and CHF, 343 ± 16; P < 0.05)—subspecies heightened ( P < 0.05) in CHF were C 18 , C 18:1 , C 20 , C 20:1 , C 20:4 , C 22:1 . Acid SMase activity was unchanged in CHF. Similarly, there were no changes in the content of either sphingosine or sphingosine‐1‐phosphate ( P > 0.05). Our data suggests that increased diaphragm ceramide content is a consequence of N‐SMase activation in CHF. Activation of N‐SMase and heightening of ceramide content may contribute to skeletal muscle weakness. Funding support: NIH 1K99HL098453‐01, 4R00HL098453‐02