Secreted Protein Acidic and Rich in Cysteine (SPARC)-Mediated Exercise Effects: Illustrative Molecular Pathways against Various Diseases

Abstract

The strong benefits of exercise, in addition to the development of both the therapeutic applications of physical activity and molecular biology tools, means that it has become very important to explore the underlying molecular patterns linking exercise and its induced phenotypic changes. Within this context, secreted protein acidic and rich in cysteine (SPARC) has been characterized as an exercise-induced protein that would mediate and induce some important effects of exercise. Herein, we suggest some underlying pathways to explain such SPARC-induced exercise-like effects. Such mechanistic mapping would not only allow us to understand the molecular processes of exercise and SPARC effects but would also highlight the potential to develop novel molecular therapies. These therapies would be based on mimicking the exercise benefits via either introducing SPARC or pharmacologically targeting the SPARC-related pathways to produce exercise-like effects. This is of a particular importance for those who do not have the ability to perform the required physical activity due to disabilities or diseases. The main objective of this work is to highlight selected potential therapeutic applications deriving from SPARC properties that have been reported in various publications.

Keywords: diseases; exercise; molecular pathways; secreted protein acidic and rich in cysteine (SPARC).

Figure 1

Possible mechanisms of protective effects of endurance training (ET) and SPARC against age-related metabolic disorders. Abbreviations: AT: adipose tissue, CVD: cardiovascular diseases, CRP: C-reactive protein, ECM: extracellular matrix, ET: endurance training, GLUT4: glucose transporter type 4, IL-6: interleukin 6, IFN: interferon, ROS: reactive oxygen species, SPARC: secreted protein acidic and rich in cysteine, T2D: type 2 diabetes, TGF-β1: transforming growth factor beta 1.

Figure 2

Possible mechanisms linking extracellular matrix (ECM), mitochondrial biogenesis, the effects of SPARC and exercise training. Abbreviations: 4E-BP1: eIF4E-binding protein 1, Akt/PKB: RAC-alpha serine/threonine-protein kinase/protein kinase B, AMP: adenosine monophosphate, AMPK: AMP-activated protein kinase, APC: adenomatous polyposis coli, ATP: adenosine triphosphate, CL-1: collagenase 1/matrix metalloproteinase 1, Dvl: dishevelled, dsh homolog 1 (Drosophila), ECM: extracellular matrix, eEF2B: eukaryotic translation elongation factor 2B, eIF2B/4B/4E: eukaryotic translation initiation factor 2B/4B/4E, Erk1/2: extracellular-signal-regulated kinases 1/2, FAK: focal adhesion kinase, GSK-3β: glycogen synthase kinase 3 beta, IGF-1: insulin-like growth factor 1, ILK: integrin-linked kinase, MEK1/2: mitogen-activated protein (MAP) kinase kinase 1/2, MNK1/2: MAP kinase-interacting kinase 1/2, mTOR: mammalian target of rapamycin, NRF-1: regulating nuclear respiratory factor 1, PGC1α: peroxisome proliferator-activated receptor gamma coactivator-1α, PI3K: phosphoinositide 3-kinase, ROS: reactive oxygen species, rpS6: ribosomal protein S6, S6K1: ribosomal protein S6 kinase beta-1, Smad3: SMAD family member 3, SPARC: secreted protein acidic and rich in cysteine, TGF-β1: transforming growth factor beta 1, TSC2: tuberous sclerosis protein 2.