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 prot ein during cardiac adaptation in simulated microgravity. Contractile force and velocity of cardiac muscle were decreased in the tail suspension rats a s compared with the control. Ca2+-dependent actomyosin ATPase activity was also decreased; however, sensitivity of cardiac muscle to Ca2+ activation w as unchanged. There was no change in expression of myosin heavy chain, trop omyosin, troponin T, or troponin I isoforms in hearts of tail suspension ra ts. A novel finding is a fragment of cardiac troponin I (cTnI) that had inc reased amounts in the heart of tail suspension rats, Binding of this cTnI f ragment by a monoclonal antibody that specifically recognizes the COOH term inus indicates an intact COOH terminus. NH2-terminal sequence analysis of t he cTnI fragment revealed truncations primarily of amino acids 1-26 and 1-2 7 and smaller amounts of 130, including Ser(23) and Ser(24), which are subs trates of protein kinase A phosphorylation, This cTnI fragment is present i n normal cardiac muscle and incorporated into myofibrils, indicating a role in regulating contractility. This proteolytic modification of cTnI up-regu lated during simulated microgravity suggests a potential role of the NH2-te rminal segment of cTnI in functional adaptations of cardiac muscle.