Intracellular and Extracellular Effects of S100B in the Cardiovascular Response to Disease

Figure 1

Schematic representation of proposed intracellular and extracellular effects of S100B in cardiac myocytes. Norepinephrine (NE) activation of the calcium-dependent protein kinase C (PKC)-𝛽, mediated by the 𝛼₁-adrenergic receptor, phosphorylates (P) transcriptional enhancer factor (1) TEF-1, resulting in DNA binding and transactivation of the 𝛽-myosin heavy chain promoter. By contrast, S100B induction by NE and other hypertrophic signals (not shown) results in calcium-dependent block of PKC-𝛽 phosphorylation of TEF-1 and inhibition of 𝛽-MHC transcription. S100B can also induce apoptosis intracellularly via a inducible nitric oxide synthase (iNOS)-NO pathway or it can be secreted and via activation of the receptor for advanced glycation end products (RAGE) (extracellular components V and CI), and induce apoptosis via MEK-ERK1/2-p53 signaling.