The relationship between cellular ion deregulation and acute and chronic toxicity

摘要: Abstract Cell injury proceeds through a predictable series of stages as it progresses from reversible to irreversible (or “point no return”) and ends eventually in cell death. Ion deregulation is strongly implicated this process and, particular, the cytosolic Ca 2+ ([Ca ] i ) which thought by most be critical step transition injury. [Ca normally maintained at approximately 100 μ m , level 10,000 times lower than for extracellular e ). Deregulation may affect any three buffering systems: plasma membrane, mitochondria, endoplasmic reticulum. Perturbation intimately related perturbation other ions, including, H + Na K . In normal cells, elevation also linked activation oncogenes well division, initiation, wound repair, differentiation, possibly tumor promotion. all models acute we have measured including ischemia, HgCl 2 calcium inophores, always became elevated. This results influx (ionomycin), redistribution intracellular stores (NEM, KCN), or both sources (HgCl The degree correlated with (as determined blebbing morphological changes) killing. More recently, much work has been focused on role neoplasia. Many stimuli, promoter TPA transforming growth factor β shown transformed cells differently. Both cause differentiation human bronchial epithelial but stimulate cells. We propose that especially plays an important role, if not key initiation chronic injury, Increases appear accelerate degradative processes unless regulated, lead