Apoptosis in the Skeletal Muscle of Rats with Heart Failure is Associated with Increased Serum Levels of TNF- and Sphingosine

Author： Dalla Libera L.   Sabbadini R.   Renken C.   Ravara B.   Sandri M.   Betto R.   Angelini A.   Vescovo G.  

Publisher： Academic Press

ISSN： 0022-2828

Source： Journal of Molecular and Cellular Cardiology, Vol.33, Iss.10, 2001-10, pp. : 1871-1878

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Skeletal muscle in congestive heart failure (CHF) is responsible for increased fatigability, decreased endurance and exercise capacity. A specific myopathy with increased expression of fast myosin heavy chains (MHCs), myocyte atrophy, secondary to myocyte apoptosis, that is triggered by high levels of circulating tumor necrosis factor (TNF- ) has been described. However, a direct effect of TNF- on skeletal muscle has not been described yet. In this paper we put forward the hypothesis that TNF- plays an indirect effect on skeletal myocytes. In an animal model of CHF, the monocrotaline-treated rat, we have observed a significant (P<0.001) increase of circulating TNF- that is paralleled by increased serum levels of the endogenous second messenger, sphingosine (SPH), (from 0.71±0.15 to 1.32±0.39 nmoles/ml, P<0.01). In the tibialis anterior (TA) muscle we found a marked increase of myocyte apoptosis (from 1.4±2.4 to 40.1±39.5 nuclei/mm3, P<0.04). We correlated plasma levels of TNF- with those of SPH and in turn with the magnitude of apoptosis. Linear regression showed a significant correlation between TNF- , SPH, and apoptosis (r2=0.74, P=0.004 andr2=0.87, P=0.001 respectively). Analysis of covariance showed that TNF- and SPH were independently correlated with the number of apoptotic nuclei (P=0.0001). In parallel in vitroexperiments, where increasing concentrations of SPH were applied to skeletal muscle cells in culture, we observed a dose-dependent increase in apoptosis. These results suggest that TNF- -induced SPH production may be responsible for skeletal muscle apoptosis. The link between TNF- and skeletal muscle apoptosis could be represented by the second messenger SPH, which can directly induce apoptosis in these cells.

Related content

Apoptosis of Skeletal Muscle Myofibers and Interstitial Cells in Experimental Heart Failure

By Vescovo G.   Zennaro R.   Sandri M.   Carraro U.   Leprotti C.   Ceconi C.   Ambrosio G.B.   Libera L.D.  

Journal of Molecular and Cellular Cardiology, Vol. 30, Iss. 11, 1998-11 ,pp. : 2449-2459 (11)

Academic Press

Access to resources Recommend Favorite

Evaluation of Skeletal Muscle Fatigue in Patients with Heart Failure

By Wilson J.R.  

Journal of Molecular and Cellular Cardiology, Vol. 28, Iss. 11, 1996-11 ,pp. : 2287-2292 (6)

Academic Press

Access to resources Recommend Favorite

Skeletal Muscle Metabolism in Experimental Heart Failure

By Bernocchi P.   Ceconi C.   Pedersini P.   Pasini E.   Curello S.   Ferrari R.  

Journal of Molecular and Cellular Cardiology, Vol. 28, Iss. 11, 1996-11 ,pp. : 2263-2273 (11)

Academic Press

Access to resources Recommend Favorite

Role of Skeletal Muscle in the Syndrome of Chronic Heart Failure

By Poole-Wilson P.A.   Ferrari R.  

Journal of Molecular and Cellular Cardiology, Vol. 28, Iss. 11, 1996-11 ,pp. : 2275-2285 (11)

Academic Press

Access to resources Recommend Favorite

Alterations in Skeletal Muscle Gene Expression in the Rat with Chronic Congestive Heart Failure

By Simonini A.   Massie B.M.   Long C.S.   Qi M.   Samarel A.M.  

Journal of Molecular and Cellular Cardiology, Vol. 28, Iss. 8, 1996-08 ,pp. : 1683-1691 (9)

Academic Press

Access to resources Recommend Favorite