Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

Figure 1

A simplified scheme of intracellular molecular mechanisms involved in fluoride toxicity and apoptosis. Nc: nucleus, ER: endoplasmic reticulum; Mt: mitochondria; RTK: receptor tyrosine kinase; GPCR: G protein-coupled receptor; FasR: Fas receptor; PI3K: phosphoinositol-3 kinase; Akt: Akt kinase; PLC: phospholipase C; PKC: protein kinase C; PIP2: phosphatidylinositol 4,5-biphosphate; IP3: inositol 1,4,5-triphosphate; DAG: diacylglycerol; CaM: calmodulin; AC: adenylyl cyclase; PKA: protein kinase A; RhoGEF: Rho guanine-nucleotide exchange factor; RhoK: Rho kinase; MLCK: myosin light chain kinase; PERK: RNA-activated protein kinase-like ER kinase; IRE1: inositol-requiring protein-1; eIF2α: eukaryotic translational initiation factor 2 subunit α; Xbp-1: X-box binding protein 1; Bip/GRP78: BiP/glucose-responsible protein 78; GADD153: DNA damage-inducible protein; PPs: protein phosphatases; K Ch: K⁺ channels; NKCC: Na⁺-K⁺-2Cl⁻ cotransport; NHE: Na⁺/H⁺ exchange.