S100a₀, (αα) protein in cardiac muscle

Abstract

SlOO protein, an acidic and calcium-binding protein, was believed to be localized in the nervous tissue, but recently it has been reported to be mainly present in the cardiac and the skeletal muscles of various mammals in the act form (S1OOao) at much higher levels than the nervous tissues. We isolated here SlOO protein from human cardiac muscles. The isolated cardiac muscle SlOO protein showed a single band on electrophoresis at the same position as that of human skeletal muscle S1OOao. The amino acid composition of the purified SlOO protein was quite similar to that of human skeletal muscle SIOOao or bovine brain S1OOao. The immunohistochemical study by use of antibodies monospecific to the a subunit of SlOO protein (S100-a) revealed that S100-a was strongly labeled in human myocardial cells, whereas the p subunit of SlOO protein (SlOO-p) was not detected in the cells.These results suggest that a predominant form of SlOO protein in human myocardial cells is not SlOOa (up) or SlOOb (pp), but SIOOao (aa). In order to determine the ultrastructural localization of SIOOao in mouse cardiac muscle, the direct peroxidase-labeled antibody method was employed. S 1 OOao was mainly localized in the polysomes in the interfibrillar spaces, the fine filamentous structure of the Z line and fascia adherens of the intercalated disc and in the lumen of junctional sarcoplasmic reticulum. SlOO protein, discovered by Moore [l], is an acidic and calcium-binding protein with a molecular mass of approximately 20 kDa, and belongs to a family of EF-hand type calcium-binding proteins [2] such as troponin C, calmodulin, parvalbumin and light-chain of myosin. SlOO protein is known to be composed of at least three forms, S1OOao, SlOOa and SlOOb, which are dimers with the subunit composition au, ap and pp respectively [3 -51. Although SlOO protein was believed to be specific to glial cells, it has been revealed immunologically that SlOO protein is also distributed in a wide variety of non-nervous cells and tissues [6, 71. Most of these immunochemical findings, however, show the localization of SlOOb rather than that of S1OOao, because the antibodies used in the previous reports were raised with a SlOO protein mixture purified from bovine brain, which is mostly composed of SlOOb and S100a. The SIOOao content in the brain is only a few percent of the total SlOO protein [8].There are a few immunohistochemical reports describing differential localization of the a subunit (S100-a) and the p subunit (SlOO-p) [9, lo]. These studies fail to reflect the precise distribution of S100-a, since immunohistochemical methods have disadvantages for quantitative analysis. We recently determined the quantitative distributions of S100-a and SlOO-p in human tissues by employing an enzyme immunoassay system consisting of specific antibodies to each subunit, and found that immunoreactive SIOOao is pre-

Cardiac adenoviral S100A1 gene delivery rescues failing myocardium

“…With regard to diastolic [Ca 2+ ] i overload that essentially contributes to impaired mitochondrial function in failing myocardium, the S100A1-mediated decrease of diastolic [Ca 2+ ] i might in part contribute to the correction of the decreased Pcr/ATP ratio. Since S100A1 has previously been shown to also reside in the outer membrane of mitochondria within cardiomyocytes (20), this finding strongly supports the notion that this Ca 2+ -binding protein might also support mitochondrial function, which is the subject of current investigations. Moreover, we speculate that the increase of free energy released from ATP hydrolysis might also restore, at least in part, depressed Na + /K + -ATPase activity in FCs (17), which might also contribute to the S100A1-mediated normalized [Na + ] i discussed above.…”

Targeting S100A1 in heart failure

“…29 During murine development, for example, cardiac S100A1 expression steadily increases and reaches a constant level in the postnatal state where it is preferentially expressed in the left ventricle and shows lower abundance in the right ventricle and the atria. 30,31 Comparative expression analysis unveiled similar cardiacpredominant expression profiles in various adult animals (mice, rat, rabbit and pig) and humans. [32][33][34] In the heart, S100A1 mainly resides in CM, with no apparent evidence for expression in cardiac fibroblasts (own unpublished data).…”

Transgenic Overexpression of the Ca2+-binding Protein S100A1 in the Heart Leads to Increased in Vivo Myocardial Contractile Performance

“…Importantly, assessment of SR Ca 2ϩ load in TG S100A1 myocytes both at rest and under ␤-AR stimulation indicates that the S100A1-mediated gain in contractility is partly caused by an enhancement in SR Ca 2ϩ content. Although S100A1 has been found to co-localize with the SR (34) and assumed to interact with SERCA (35), co-immunoprecipitation with TG S100A1 and NLC hearts so far revealed no evidence for a direct interaction of S100A1 with either SERCA2a or PLB. Thus, further studies will have to clarify whether S100A1 may directly affect cardiac SERCA activity or enhance SR Ca 2ϩ load by a SERCA2a-independent mechanism.…”