S100B's double life: Intracellular regulator and extracellular signal

Abstract

The Ca2+-binding protein of the EF-hand type, S100B, exerts both intracellular and extracellular functions. Recent studies have provided more detailed information concerning the mechanism(s) of action of S100B as an intracellular regulator and an extracellular signal. Indeed, intracellular S100B acts as a stimulator of cell proliferation and migration and an inhibitor of apoptosis and differentiation, which might have important implications during brain, cartilage and skeletal muscle development and repair, activation of astrocytes in the course of brain damage and neurodegenerative processes, and of cardiomyocyte remodeling after infarction, as well as in melanomagenesis and gliomagenesis. As an extracellular factor, S100B engages RAGE (receptor for advanced glycation end products) in a variety of cell types with different outcomes (i.e. beneficial or detrimental, pro-proliferative or pro-differentiative) depending on the concentration attained by the protein, the cell type and the microenvironment. Yet, RAGE might not be the sole S100B receptor, and S100B's ability to engage RAGE might be regulated by its interaction with other extracellular factors. Future studies using S100B transgenic and S100B null mice might shed more light on the functional role(s) of the protein.

S100B Inhibition Reduces Behavioral and Pathologic Changes in Experimental Traumatic Brain Injury

“…As an intracellular regulator, S100B stimulates cell proliferation and migration, inhibits apoptosis and differentiation, and activation of astrocytes, which may have implications for brain repair after central nervous system (CNS) injury. 6 In contrast, as an extracellular factor S100B interacts with advanced glycation end product-specific receptor (AGER) to exert beneficial or detrimental effects, or pro-proliferative or pro-differentiative consequences based on its concentration and microenvironment. 7,8 In addition to its expression in astroglia and Schwann cells, S100B has also been found in adipocytes, chondrocytes, cardiomyocytes, lymphocytes, bone marrow cells, and melanocytes where it exerts intracellular and extracellular functions.…”

“…7,8 In addition to its expression in astroglia and Schwann cells, S100B has also been found in adipocytes, chondrocytes, cardiomyocytes, lymphocytes, bone marrow cells, and melanocytes where it exerts intracellular and extracellular functions. 6 Therefore, both CNS and circulatory S100B exert the same functions that are dependent on their concentration and may serve as important biomarkers of CNS injury. Intracellular S100B interaction with Src kinase activates phosphoinositide 3-kinase signaling and downstream RhoA/Rackdependent stress fiber formation as well as glycogen synthase kinase 3β/Rho-dependent stellation.…”

The developing landscape of diagnostic and prognostic biomarkers for spinal cord injury in cerebrospinal fluid and blood

“…S100 is involved in a diverse range of functions including calcium homeostasis, 396 enzyme activity and metabolism, cell proliferation and differentiation (80). Measurement of S100β 397 has potential as an acute marker of SCI, as it is significantly increased in the blood (76,77,81) and 398 CSF (76) of rats at 6h after severe contusion injury compared to sham injury.…”

S100B protein in serum is elevated after global cerebral ischemic injury

“…However, some other cells outside the brain, like kidney epithelial cells, ependymocytes, chondrocytes, adipocytes, and melanocytes, can also express S100B protein. [2,3]…”