A Proteolytic NH2-terminal Truncation of Cardiac Troponin I That Is Up-regulated in Simulated Microgravity

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. Ca2+-dependent actomyosin ATPase activity was also decreased; however, sensitivity of cardiac muscle to Ca2+ 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. NH2-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 Ser23 and Ser24, 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 NH2-terminal segment of cTnI in functional adaptations of cardiac muscle. 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. Ca2+-dependent actomyosin ATPase activity was also decreased; however, sensitivity of cardiac muscle to Ca2+ 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. NH2-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 Ser23 and Ser24, 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 NH2-terminal segment of cTnI in functional adaptations of cardiac muscle. troponin C cardiac troponin I extensor digitorum longus monoclonal antibody myosin heavy chain polyacrylamide gel electrophoresis pCa required for half-maximal activation cAMP-dependent protein kinase Tris-buffered saline tropomyosin troponin I troponin T 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. Through neurohumoral regulations, this fluid redistribution induces reductions of blood volume and central venous pressure (1Convertino V. Hoffler G.W. J. Fla. Med. Assoc. 1992; 79: 517-524PubMed Google Scholar). Although decreased intrapleural pressure during space flight may assist filling of the heart (2White R.J. Blomqvist C.G. J. Appl. Physiol. 1998; 85: 738-746Crossref PubMed Scopus (67) Google Scholar), prolonged exposure to microgravity results in decreases in cardiac preload and function, evident by echocardiography of astronauts showing decreases in left ventricular end diastolic volume and ventricular stroke volume (3Bungo M.W. Goldwater D.J. Popp R.L. Sandler H. J. Appl. Physiol. 1987; 62: 278-283Crossref PubMed Scopus (64) Google Scholar, 4Herault S. Fomina G. Alferova I. Kotovskaya A. Poliakov V. Arbeille P. Eur. J. Physiol. 2000; 81: 384-390Crossref Scopus (117) Google Scholar). Rats flown in space for 14 days showed decreased average cross-sectional area of the myocytes in left ventricular muscle, indicating myocardial atrophy (5Goldstein M.A. Edwards R.J. Schroeter P. J. Appl. Physiol. 1992; 73 (suppl.): 94-100Crossref Google Scholar). These observations suggest that prolonged exposure to microgravity induces a decrease in cardiac function. However, the regulation of cardiac muscle contractility in microgravity is unclear. In addition to the health and safety of astronauts during and after long space flight, a thorough understanding of the adaptation of cardiac muscle in microgravity will also contribute to the prevention and treatment of myocardial dysfunction in chronic bedridden, paraplegic, and heart failure patients, since similar changes are seen in their hearts (6Kashihara H. Haruna Y. Suzuki Y. Kawakubo K. Takenaka K. Bonde-Petersen F. Gunji A. Acta Physiol. Scand. Suppl. 1994; 616: 19-26PubMed Google Scholar, 7Kessler K.M. Pina I. Green B. Burnett B. Laighold M. Bilsker M. Palomo A.R. Myerburg R.J. Am. J. Cardiol. 1986; 58: 525-530Abstract Full Text PDF PubMed Scopus (99) Google Scholar, 8Dunlap A.W. Thomason D.B. Menon V. Hofmann P.A. J. Appl. Physiol. 1996; 80: 1612-1617Crossref PubMed Scopus (5) Google Scholar). The adaptation of myocardial contractility in microgravity may involve structural and functional modifications of contractile proteins. The contraction of cardiac muscle is based on actin-myosin interactions regulated by intracellular Ca2+ via the thin filament-based troponin-tropomyosin system (9Gordon A.M. Homsher E. Regnier M. Physiol. Rev. 2000; 80: 853-924Crossref PubMed Scopus (1342) Google Scholar). The regulation of thin filament proteins may play a role in the functional adaptation of cardiac muscle. The troponin complex contains three subunits: the Ca2+-binding subunit troponin C (TnC),1 the tropomyosin (Tm)-binding subunit troponin T (TnT), and the inhibitory subunit troponin I (TnI) (10Leavis P.C. Gergely J. CRC Crit. Rev. Biochem. 1984; 16: 235-305Crossref PubMed Scopus (326) Google Scholar, 11Tobacman L.S. Annu. Rev. Physiol. 1996; 58: 447-481Crossref PubMed Scopus (461) Google Scholar). During muscle contraction, Ca2+-induced interactions between TnC and TnI, TnT, Tm, and actin result in a series of allosteric conformational changes in the thin filament, translating the signal into the activation of actomyosin ATPase and development of force (10Leavis P.C. Gergely J. CRC Crit. Rev. Biochem. 1984; 16: 235-305Crossref PubMed Scopus (326) Google Scholar). A key step in this signaling mechanism is the release of inhibition of TnI on actin-myosin interaction (12Perry S.V. Mol. Cell Biochem. 1999; 190: 9-32Crossref PubMed Google Scholar). Three homologous TnI genes (cardiac, fast skeletal muscle, and slow skeletal muscle) have evolved in vertebrates to encode the muscle type-specific TnI isoforms (13Hastings K.E.M. Cell Struct. Funct. 1997; 22: 205-211Crossref PubMed Scopus (43) Google Scholar). Expression of TnI isoforms is regulated during development. The embryonic heart expresses exclusively slow skeletal muscle TnI. During perinatal heart development, the expression level of slow TnI decreases, and expression of cardiac TnI (cTnI) increases and becomes the only TnI isoform in the adult heart (14Saggin L. Gorza L. Ausoni S. Schiaffino S. J. Biol. Chem. 1989; 264: 16299-16302Abstract Full Text PDF PubMed Google Scholar, 15Murphy A.M. Jones L. Sims H.F. Strauss A.W. Biochemistry. 1991; 30: 707-712Crossref PubMed Scopus (99) Google Scholar, 16Jin J.P. Biochem. Biophys. Res. Commun. 1996; 225: 883-889Crossref PubMed Scopus (59) Google Scholar). Primary structures of cardiac, slow, and fast skeletal muscle TnI isoforms have been determined from cDNA and genomic cloning and sequencing (15Murphy A.M. Jones L. Sims H.F. Strauss A.W. Biochemistry. 1991; 30: 707-712Crossref PubMed Scopus (99) Google Scholar, 17Baldwin Jr., A.S. Kittler E.L. Emerson Jr., C.P. Proc. Natl. Acad. Sci. U. S. A. 1985; 82: 8080-8084Crossref PubMed Scopus (59) Google Scholar, 18Koppe R.I. Hallauer P.L. Karpati G. Hastings K.E. J. Biol. Chem. 1989; 264: 14327-14333Abstract Full Text PDF PubMed Google Scholar, 19Martin A.F. Orlowski J. J. Mol. Cell. Cardiol. 1991; 23: Full Text PDF PubMed Scopus Google Scholar, Y. P.C. S. PubMed Scopus Google Scholar, S. M. A. P. M. Schiaffino S. J. Biol. Chem. 1994; Full Text PDF PubMed Google Scholar, L. P. L. J. Biol. Chem. 1994; Full Text PDF PubMed Google Scholar, 1996; PubMed Scopus Google Scholar). regulation of TnI and been to involve amino chain modification and of the A proteolytic of amino acids of the COOH terminus of cTnI been during myocardial and Res. 1999; PubMed Scopus Google Scholar). Expression of this cTnI fragment in myocardial A.M. H. E. 2000; PubMed Scopus Google Scholar). A significant between cTnI and skeletal muscle is an NH2-terminal of amino acids in cTnI (12Perry S.V. Mol. Cell Biochem. 1999; 190: 9-32Crossref PubMed Google Scholar). The signaling of and in the NH2-terminal of cTnI by cAMP-dependent protein kinase J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). This of cTnI decreases myofilament by the Ca2+ of TnC R.J. J. Biol. Chem. Full Text PDF PubMed Google Scholar). This mechanism an role in the functional adaptation of cardiac muscle to or stress P.A. 1997; PubMed Scopus Google Scholar, M. 1999; PubMed Scopus Google Scholar). The present investigated the role of myofilament proteins in the adaptation of myocardial contractility in a rat tail suspension of simulated microgravity E. Scholar). of tail suspension in decreases of cardiac muscle contractility change in the expression of contractile and protein However, a novel finding is an NH2-terminal cTnI fragment with increased amounts in the heart of tail suspension rats. This proteolytic NH2-terminal modification of cTnI the that are This regulation in simulated microgravity suggests a role of the NH2-terminal of cTnI in functional adaptations of cardiac muscle. rats were into and tail suspension The rats were in a to and and suspension was by a E. for or was to the tail and the of the rats was during the Rats were with The heart was and in and The left ventricular muscle was and in a to the A. J. Am. J. Physiol. Google Scholar). The muscle was with and was to the a series of to a of The was and with The end of the muscle was by a The end was to a to an force The were by The was after a of for The of the muscle was increased a force was The was by the muscle from the to of the and of the step changes in was after a sequence of to of the end of the was and the muscle was and The cross-sectional area of the muscle was the of a with a of A. J. Am. J. Physiol. Google Scholar). was by cross-sectional The velocity of was from to the of muscle M. V. Am. J. Physiol. PubMed Google Scholar). cardiac muscle in and in were from the muscle of left a The were as for the of for the was to The were with for in a and A was to the muscle was The for the cardiac muscle was by to the to a series of pCa and were The in the were the of Ca2+ to the A. F. J. Physiol. PubMed Scopus Google Scholar). The was to the The were to a in which force and are A. F. J. Physiol. PubMed Scopus Google Scholar). cardiac were as K.M. J. Appl. Physiol. 1987; PubMed Scopus Google Scholar). The protein was determined by the Biochem. PubMed Scopus Google Scholar). The ATPase activity of the was in a The was by the addition of and was after by the addition of an volume of the was as K.M. J. Appl. Physiol. PubMed Scopus (43) Google Scholar). J. Physiol. 1999; PubMed Scopus Google Scholar), protein was from rat ventricular muscle by in gel electrophoresis The myocardial protein were by gel with an of was for the analysis of myosin heavy chain gel with an of was for the of and and gel with an of was for the of TnI. The protein by were to for The was in Tris-buffered saline for The was with monoclonal and PubMed Scopus Google Scholar), an A. Am. J. Physiol. 2000; PubMed Google Scholar), an M. A. Biochemistry. PubMed Scopus Google Scholar), a J.P. Biochem. Biophys. Res. Commun. 1996; 225: 883-889Crossref PubMed Scopus (59) Google Scholar), or an from of 1985; PubMed Scopus Google in with and and the was with or antibody in for as was as M. A. Biochemistry. PubMed Scopus Google to the expression of TnT, TnI, and isoforms in the cardiac muscle. cTnI was by the an the COOH terminus of TnI M. A. Biochemistry. PubMed Scopus Google Scholar). The was from fluid a and to to the The of cTnI was a left ventricular muscle was into and by of and on for for the myosin was The was in of by on for as the was in and on the in The was with and the proteins to the were with were into of The were by and as to the cTnI The cTnI by were and and The protein was in on and a as The was by and a protein the cTnI fragment was NH2-terminal amino sequencing was by an amino the the of analysis of the was to the amounts of the Tm, TnT, TnI, and the TnI fragment in the cardiac muscle of tail suspension and rats. the the were on a the The of the protein by the was from of tail suspension and rat heart are as The of between the was by The and of rat cTnI and were from amino the The body of the rats were similar to The heart and left ventricular pressure of the tail suspension rats were from the The heart and the of muscle of the tail suspension rats were also from of the rats force on the of and rats showed no in In was decreased in the cardiac muscle of the tail suspension rats This decrease of tail suspension and significant of tail However, the was in the cardiac muscle of tail suspension similar to that seen in the cardiac muscle J. S. U. H. Res. 1998; PubMed Google Scholar, J. Res. 2000; PubMed Scopus Google Scholar). The of the muscle was also decreased after of tail suspension with a prolonged to development the decreased force and the and of intact muscle to the Ca2+ were from indicating that the Ca2+ of was in the tail suspension rats Res. 2000; PubMed Scopus Google Scholar). The of cardiac muscle showed no between from the tail suspension and rats The from the was also However, with the results from intact cardiac muscle, the force of the cardiac muscle was decreased in the tail suspension rats the ATPase activity of the cardiac of tail suspension rats was that of the rats Expression of isoforms of the contractile and proteins was to isoform contribute to the decrease in the cardiac muscle contractility in the tail rats. to and and PubMed Scopus Google Scholar), the in no decrease in the or expression of in the ventricular muscle of tail suspension rats. The results in that the the that recognizes and only the in the heart of and tail suspension rats with no from the The the and slow skeletal muscle showed only adult cardiac TnT, indicating no change in the expression of cardiac isoforms J. Biol. Chem. Full Text PDF PubMed Google in the heart of and tail suspension rats. the antibody cardiac and skeletal muscle showed no expression of fast or slow skeletal muscle isoforms in the heart of tail suspension rats. proteolytic fragment of and was in the tail suspension rat hearts by three TnI isoforms M. A. Biochemistry. PubMed Scopus Google fast and slow skeletal muscle TnI isoforms in the heart of tail suspension rats A novel finding was a TnI fragment with increased amounts in the heart of rats In addition to the from from recognizes this on from in the This is also by a J.P. Biochem. Biophys. Res. Commun. 1996; 225: 883-889Crossref PubMed Scopus (59) Google Scholar), that is a TnI The of hearts of and rats rat extensor digitorum longus a fast skeletal slow skeletal and cardiac muscle showed that the cTnI the slow skeletal muscle TnI the fast skeletal muscle TnI Although slow skeletal muscle TnI is in embryonic and cardiac (14Saggin L. Gorza L. Ausoni S. Schiaffino S. J. Biol. Chem. 1989; 264: 16299-16302Abstract Full Text PDF PubMed Google Scholar, 15Murphy A.M. Jones L. Sims H.F. Strauss A.W. Biochemistry. 1991; 30: 707-712Crossref PubMed Scopus (99) Google Scholar, 16Jin J.P. Biochem. Biophys. Res. Commun. 1996; 225: 883-889Crossref PubMed Scopus (59) Google Scholar), the gel indicates that this TnI is a of slow skeletal muscle TnI in the adult Although may also the of TnI in we have by amino sequencing that this TnI is a cTnI a was in the heart of tail suspension rats as compared with amounts of this cTnI fragment increased in the heart of tail suspension rats. The of the cTnI in hearts of tail suspension rats was by of the The results an of the cTnI fragment from to of the cTnI an of to intact cTnI from to Although the cTnI fragment increased this only of the no significant change in the amounts of intact cTnI was by analysis of the amounts of cardiac and cTnI in the heart of and tail suspension rats. of on cardiac muscle revealed increased amounts of the cTnI fragment in the heart of tail suspension no change in the of Tm, cardiac and intact cTnI was The was the of rat hearts as the between the cTnI fragment and intact cTnI in the heart of tail suspension and rats are are for and for cTnI fragment and during the of the contribute to the amounts of the cTnI this analysis of heart a series of showed no in the of the cTnI fragment during a of to showed that of rat heart in as Proc. Natl. Acad. Sci. U. S. A. 1999; PubMed Scopus Google change the of the cTnI fragment These results that the cTnI fragment with an increased level in the heart of tail suspension rats is a of protein In may a regulated of cTnI in the cardiac muscle and may play a role during the functional adaptation in simulated microgravity. The of the cTnI fragment by the terminus was as as that for the intact cTnI the the fragment M. A. Biochemistry. PubMed Scopus Google Scholar), this result indicates an intact COOH terminus in the cTnI NH2-terminal sequence analysis showed that were three of cTnI by truncations the of amino acids or The were the of amino acids 1–26 and 1–27 and These to of the cTnI the cTnI fragment is by by proteolytic This of cTnI chain the and the terminus and a of the NH2-terminal The of the three NH2-terminal cTnI is in with the in the and and the of an intact COOH amino sequence of the cTnI of rat fast skeletal muscle TnI, slow skeletal muscle TnI, and cTnI are with the for the of TnT, and actin as as the inhibitory The by of the three TnI genes are by the The is by a The three NH2-terminal determined from the rat cTnI fragment are and with the sequence by of the rat cTnI A.M. Jones Biochem. J. 1997; PubMed Scopus Google Scholar). The the three The and of the NH2-terminal rat cTnI of amino sequence between the three NH2-terminal and intact cTnI are in in a The sequence between the three NH2-terminal and intact cTnI are in The structural of cardiac, slow, and fast skeletal muscle that the NH2-terminal cTnI the homologous to the skeletal muscle of the for thin filament proteins. been that of the NH2-terminal amino a significant change in the inhibitory of J. A.M. R.J. J. Biol. Chem. 1994; Full Text PDF PubMed Google Scholar). may that the cTnI fragment by the NH2-terminal amino acids in the thin filament with this analysis of rat cardiac showed that the of the NH2-terminal cTnI fragment into the is with that of intact to their in the cardiac muscle The three have similar and in their structural and functional The in and that normal rat and cardiac significant amounts of the NH2-terminal the COOH terminus analysis of cardiac muscle from a of revealed similar cTnI in of the hearts These suggest that the proteolytic NH2-terminal of cTnI a regulation of myocardial with the of the NH2-terminal an structural of the cTnI is the of Ser23 and in intact cTnI J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. K. M. J. J. Res. Cell 1998; PubMed Scopus Google Scholar). The present investigated the adaptation of cardiac muscle in simulated microgravity the tail suspension rat The head of the rats a redistribution of body fluid toward the The changes in the tail suspension rats are similar to in astronauts during space flight (1Convertino V. Hoffler G.W. J. Fla. Med. Assoc. 1992; 79: 517-524PubMed Google Scholar). a of simulated on the rats have been to the of microgravity on the cardiovascular system (1Convertino V. Hoffler G.W. J. Fla. Med. Assoc. 1992; 79: 517-524PubMed Google Scholar, 8Dunlap A.W. Thomason D.B. Menon V. Hofmann P.A. J. Appl. Physiol. 1996; 80: 1612-1617Crossref PubMed Scopus (5) Google Scholar, Med. 1985; Google Scholar, M. M. M.A. 2000; 22: PubMed Scopus Google Scholar). The tail suspension in this the of tail to the stress on the In addition to a long tail suspension this that may with the of the cardiovascular The results that this of simulated changes in the contractility of cardiac muscle and in of the cardiac myofilament the tail suspension a system to the mechanism for and myocardial In of tail suspension a significant change in cardiac muscle contractile force similar to the results from a A.W. Thomason D.B. Menon V. Hofmann P.A. J. Appl. Physiol. 1996; 80: 1612-1617Crossref PubMed Scopus (5) Google Scholar). In of tail suspension in a significant decrease in cardiac muscle contractility. the heart and left ventricular pressure were the of the cardiac muscle was decreased in the tail suspension rats The was also decreased a prolonged to development. However, the of the of cardiac muscle, which the for the was in the tail suspension rats the decreased myocardial contractility and volume preload may contribute to the cardiac seen in long exposure to microgravity. Although the ATPase activity was in the cardiac muscle of the tail suspension rats was no change in the expression of isoforms the decrease in contractility to changes in myosin in the In no change in the expression of Tm, TnT, and TnI isoforms was in the heart of rats been by that contractile and protein isoforms are for the change of muscle or S. Physiol. Rev. 1996; PubMed Scopus Google Scholar). In to the of cardiac genes in the adult ventricular muscle in heart S. H. Med. 1998; PubMed Scopus Google Scholar), the lack of isoform of Tm, TnT, and TnI in the hearts of tail suspension rats indicates no change in cardiac muscle or during the functional adaptation in simulated microgravity. A novel finding of the present is the NH2-terminal cTnI fragment in normal and rat hearts and modification of cTnI been with on myocardial contractility. Ca2+ in by may proteolytic of cTnI amino to the COOH terminus Res. 1999; PubMed Scopus Google Scholar). The fragment the of the and a in the hearts of A.M. H. E. 2000; PubMed Scopus Google Scholar). The cTnI in an intact COOH terminus as by to the terminus that M. A. Biochemistry. PubMed Scopus Google Scholar). with in normal cardiac muscle, the and normal into the myofilament of this NH2-terminal of cTnI suggest a This is by the that a similar cTnI fragment is also in hearts the increased amounts of the NH2-terminal cTnI in the heart of rats may a functional adaptation of cardiac muscle in simulated microgravity and a proteolytic regulation of cardiac proteins. The mechanism of the proteolytic NH2-terminal of cTnI cTnI that is regulated by and protein kinase C of cTnI F. F. E. Schiaffino S. S. Biochem. J. PubMed Scopus Google may play an The cTnI of the NH2-terminal the functional of the NH2-terminal cTnI may to the of skeletal muscle TnI as as to the Expression of slow skeletal muscle TnI in the heart of in an increased sensitivity to Ca2+ which was by in the treatment H. A.F. R.J. R.L. J. Physiol. 1999; PubMed Scopus Google Scholar). an may the Ca2+ sensitivity of the cardiac muscle in the rats. However, the of the NH2-terminal cTnI on cardiac muscle contraction that of slow skeletal muscle TnI, sequence is present between the homologous of cTnI and slow TnI M. A. Biochemistry. PubMed Scopus Google Scholar), which may also result in in function. This is by the that a of the NH2-terminal of the cTnI chain with the NH2-terminal of slow skeletal muscle TnI in contractility from of cTnI or slow TnI J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). the NH2-terminal cTnI may a functional change in the cardiac thin the NH2-terminal segment of cTnI contains the Ser23 and which are substrates for J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, R.J. J. Biol. Chem. Full Text PDF PubMed Google Scholar). of in cTnI may of Ser23 a decrease in the sensitivity of the to Ca2+ via a of K. K. M. J. J. Res. Cell 1998; PubMed Scopus Google Scholar). The of a of the NH2-terminal cTnI in the cardiac muscle may a level of that is regulated by the signaling the of the NH2-terminal cTnI in the heart of tail suspension rats may cardiac muscle contractility by the of of Ser23 and on the sensitivity of thin filament to complex neurohumoral regulation during cardiac the contractility of the cardiac muscle, this mechanism may have to the Ca2+ sensitivity in the cardiac muscle of tail suspension rats the contractile force and velocity were decreased and The of the NH2-terminal cTnI in the heart of tail suspension rats indicates that the of thin filament may play a role in the adaptation of cardiac muscle in microgravity. the proteolytic modification of cTnI may the of the cardiac muscle to regulation that an role in myocardial adaptations to and R.J. PubMed Scopus Google Scholar, Hoffler G.W. Blomqvist C.G. Am. J. Physiol. 1997; Google Scholar, I. M. Am. J. Physiol. 1997; Google Scholar). is that the blood pressure and left ventricular pressure are in the tail suspension and the may a regulation the the neurohumoral regulation in the rat cardiac in simulated microgravity. The of the NH2-terminal from cTnI may a of the cardiac muscle thin filament, which may in cardiac during prolonged exposure to microgravity. the NH2-terminal of cTnI a novel proteolytic regulation of cardiac muscle contractility. This finding suggests that a inhibition of the NH2-terminal of cTnI may a potential for the prevention of cardiovascular dysfunction of astronauts during and after long space the sensitivity of cardiac myofilament to Ca2+ activation the proteolytic modification of cTnI may also play a role in myocardial adaptation and as in chronic bedridden, paraplegic, and heart failure K.M. Pina I. Green B. Burnett B. Laighold M. Bilsker M. Palomo A.R. Myerburg R.J. Am. J. Cardiol. 1986; 58: 525-530Abstract Full Text PDF PubMed Scopus (99) Google Scholar, P.A. 1997; PubMed Scopus Google Scholar, M. 1999; PubMed Scopus Google Scholar, H. K. A. K. K. H. J. M. J. 1992; PubMed Scopus (5) Google Scholar). for the for the rat heart and for and of this