Review articleS100A1 in cardiovascular health and disease: Closing the gap between basic science and clinical therapy
Section snippets
S100A1 genomic organization
S100A1 is a member of the multigenic S100 protein family constituting by far the largest subgroup within the EF-hand Ca2+ binding protein superfamily [6], [24]. These proteins were first discovered in 1965 by B.W. Moore and characterized as “S100”, accounting for their solubility in a 100%-saturated solution with ammonium sulphate [24]. Since then S100 proteins have emerged as regulators of fundamental cellular and molecular functions, including cell proliferation, differentiation, survival and
S100A1 expression in cardiomyocytes
S100A1 is preferentially expressed in human cardiac muscle but also found in skeletal muscle, brain and kidney (most recent expression profiles are accessible through http://www.genecards.org/cgi-bin/carddisp.pl?gene=S100A1&search=S100A1), albeit at much lower concentrations. Comparative analyses revealed a similar S100A1 expression pattern in rodents and larger mammals [34], [35], [36], [37], [38]. Heizmann's group showed that S100A1 mRNA and protein levels steadily increase in the developing
S100A1 in cardiac disease
Chronically dysfunctional human myocardium is characterized by progressively diminished S100A1 mRNA and protein levels that inversely correlate with the severity of the disease [67]. Given the same pathological plasticity in chronically diseased rodent, rabbit and pig hearts [13], [49], [58], [59], [60], [68], decreased S100A1 expression seems to be a common pathognomonic molecular signature of failing myocardium. Abnormal in vivo cardiac S100A1 expression has been recapitulated in vitro by
Conclusions and future perspective
In recent years, S100A1 has clearly emerged as a critical regulator of Ca2+ handling and NO homeostasis in cardiac and vascular cells reflected by numerous reports highlighting its physiological and pathophysiological relevance in the cardiovascular system (reviewed in [4], [21]). However, S100A1 appears to have a likewise significant role in skeletal muscle function although its pathophysiological and therapeutic relevance in congenital and HF-associated skeletal muscle disorders have not been
Acknowledgements
This article was supported by grants from the NIH (R01 HL92130 to P. Most), DFG (562/1-1 to P. Most and S.T. Pleger) and BMBF (01GU0527 to P. Most).
References (77)
- et al.
S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature)
Biochem. Biophys. Res. Commun.
(2004) - et al.
S100A12 (EN-RAGE) in monitoring Kawasaki disease
Lancet
(2003) - et al.
The ischemic rat heart releases S100B
Life Sci.
(2005) - et al.
Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells
Blood
(2005) - et al.
Expression of S100A6 in cardiac myocytes limits apoptosis induced by tumor necrosis factor-alpha
J. Biol. Chem.
(2008) - et al.
S100A6 is a negative regulator of the induction of cardiac genes by trophic stimuli in cultured rat myocytes
Exp. Cell Res.
(2005) - et al.
Targeting myocardial beta-adrenergic receptor signaling and calcium cycling for heart failure gene therapy
J. Card. Fail.
(2007) A soluble protein characteristic of the nervous system
Biochem. Biophys. Res. Com.
(1965)Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type
Biochim. Biophys. Acta
(1999)- et al.
The three-dimensional solution structure of Ca2+-bound S100A1 as determined by NMR spectroscopy
J. Mol. Biol.
(2005)
Hydrophobic residues in the C-terminal region of S100A1 are essential for target protein binding but not for dimerization
Cell Calcium
Redox modifications of the C-terminal cysteine residue cause structural changes in S100A1 and S100B proteins
Biochem. Biophys. Acta
Transcriptional regulation of S100A1 and expression during mouse heart development
Biochim. Biophys. Acta
Isolation of a rat S100 alpha cDNA and distribution of its mRNA in rat tissues
Brain Res. Bull.
S100ao (alpha alpha) protein is mainly located in the heart and striated muscles
Biochim. Biophys. Acta
S100A1 increases the gain of excitation–contraction coupling in isolated rabbit ventricular cardiomyocytes
J. Mol. Cell. Cardiol.
Ca(2+)-dependent interaction of S100A1 with the sarcoplasmic reticulum Ca(2+)-ATPase2a and phospholamban in the human heart
Biochem. Biophys. Res. Commun.
Transgenic overexpression of the Ca2+ binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance
J. Biol. Chem.
S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes
Cell Calcium
S100A1 binds to the calmodulin-binding site of ryanodine receptor and modulates skeletal muscle excitation–contraction coupling
J. Biol. Chem.
S100A1 and calmodulin compete for the same binding site on ryanodine receptor
J. Biol. Chem.
Cardiac energy metabolism homeostasis: role of cytosolic calcium
J. Mol. Cell. Cardiol.
Titin–actin interaction in mouse myocardium: passive tension modulation and its regulation by calcium/s100a1
Biophys. J.
S100A1 gene therapy preserves in vivo cardiac function after myocardial infarction
Mol. Therapy
Interaction of isoforms of S100 protein with smooth muscle caldesmon
FEBS Let.
The C-terminus (aa 75–94) and the linker region (aa 42–54) of the Ca2+ binding protein S100A1 differentially enhance sarcoplasmic Ca2+ release in murine skinned skeletal muscle fibres
J. Biol. Chem.
A noncontiguous, intersubunit binding site for calmodulin on the skeletal muscle Ca2+ release channel
J. Biol. Chem.
Altered expression of the Ca(2+)-binding protein S100A1 in human cardiomyopathy
Biochim. Biophys. Acta
Right ventricular upregulation of the Ca(2+) binding protein S100A1 in chronic pulmonary hypertension
Biochim. Biophys. Acta
Extracellular S100A1 protein inhibits apoptosis in ventricular cardiomyocytes via activation of the extracellular-regulated kinase (ERK1/2) pathway
J. Biol. Chem.
S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles
Int. J. Biochem. Cell. Biol.
Calcium signalling in endothelial cells
Cardiovasc. Res.
Calcium cycling and signaling in cardiac myocytes
Ann. Rev. Physiol.
Intracellular and extracellular roles of S100 proteins
Microsc. Res. Tech.
S100A1: a novel inotropic regulator of cardiac performance. Transition from molecular physiology to pathophysiological relevance
Am. J. Physiol.
Calcium-dependent and -independent interactions of the S100 protein family
Biochem. J.
S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products
Circ. Res.
Increased proinflammatory endothelial response to S100A8/A9 after preactivation through advanced glycation end products
Cardiovasc. Diabet.
Cited by (61)
Binding and Functional Folding (BFF): A Physiological Framework for Studying Biomolecular Interactions and Allostery
2022, Journal of Molecular BiologyIntracavernosal Adeno-Associated Virus-Mediated S100A1 Gene Transfer Enhances Erectile Function in Diabetic Rats by Promoting Cavernous Angiogenesis via VEGF-A/VEGFR2 Signaling
2019, Journal of Sexual MedicineCitation Excerpt :Furthermore, our data suggested that administration of exogenous S100A1 could activate pro-angiogenic factors, augment endothelial content, and eventually partially ameliorate erectile function in rats with streptozotocin-induced diabetes.34 Although the role of S100A1 with respect to cardiovascular pathophysiology has been described,10–12 its role in ED is unknown. Our previous work noted that APO-positive rats had only mild to moderate ED, whereas APO-negative rats’ sexual function was severely impaired.19
Molecular Basis of S100A1 Activation at Saturating and Subsaturating Calcium Concentrations
2016, Biophysical JournalThe interplay of inflammation, exosomes and Ca<sup>2+</sup> dynamics in diabetic cardiomyopathy
2023, Cardiovascular Diabetology