Abstract
In a tail suspension rat model, we investigated changes in myofilament protein during cardiac adaptation in simulated microgravity. Contractile force and velocity of cardiac muscle were decreased in the tail suspension rats as compared with the control. Ca(2+)-dependent actomyosin ATPase activity was also decreased; however, sensitivity of cardiac muscle to Ca(2+) activation was unchanged. There was no change in expression of myosin heavy chain, tropomyosin, troponin T, or troponin I isoforms in hearts of tail suspension rats. A novel finding is a fragment of cardiac troponin I (cTnI) that had increased amounts in the heart of tail suspension rats. Binding of this cTnI fragment by a monoclonal antibody that specifically recognizes the COOH terminus indicates an intact COOH terminus. NH(2)-terminal sequence analysis of the cTnI fragment revealed truncations primarily of amino acids 1-26 and 1-27 and smaller amounts of 1-30, including Ser(23) and Ser(24), which are substrates of protein kinase A phosphorylation. This cTnI fragment is present in normal cardiac muscle and incorporated into myofibrils, indicating a role in regulating contractility. This proteolytic modification of cTnI up-regulated during simulated microgravity suggests a potential role of the NH(2)-terminal segment of cTnI in functional adaptations of cardiac muscle.
Highlights
In microgravity, a significant stress on the cardiovascular system is the redistribution of body fluid toward the head due to the lack of hydrostatic pressure
1 The abbreviations used are: TnC, troponin C; cardiac TnI (cTnI), cardiac troponin I; EDL, extensor digitorum longus; monoclonal antibodies (mAbs), monoclonal antibody; MHC, myosin heavy chain; PAGE, polyacrylamide gel electrophoresis; pCa50, pCa required for half-maximal activation; PKA, cAMP-dependent protein kinase; TBS, Tris-buffered saline; Tm, tropomyosin; TnI, troponin I; TnT, troponin T
Isometric force measurements on the papillary muscles of tail-suspended and control rats showed no difference in resting tension (RT) (Fig. 1A)
Summary
TnC, troponin C; cTnI, cardiac troponin I; EDL, extensor digitorum longus; mAb, monoclonal antibody; MHC, myosin heavy chain; PAGE, polyacrylamide gel electrophoresis; pCa50, pCa required for half-maximal activation; PKA, cAMP-dependent protein kinase; TBS, Tris-buffered saline; Tm, tropomyosin; TnI, troponin I; TnT, troponin T. A novel finding is an NH2terminal truncated cTnI fragment with increased amounts in the heart of tail suspension rats This proteolytic NH2-terminal modification of cTnI removes the two serine residues that are PKA substrates. This post-translational regulation in simulated microgravity suggests a role of the NH2-terminal domain of cTnI in functional adaptations of cardiac muscle
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