Nerve growth factor induces Na+,K+-ATPase in a nerve cell line.
The effects of nerve growth factor (NGF) on induction of Na+,K+-ATPase were examined in a rat pheochromocytoma cell line, PC12h. Na+,K+-ATPase activity in a crude particulate fraction from the cells increased from 0.37 +/- 0.02 (n = 19) to 0.55 +/- 0.02 (n = 20) (means +/- SEM, mumol Pi/min/mg of protein) when cultured with NGF for 5-11 days. The increase caused by NGF was prevented by addition of specific anti-NGF antibodies. Epidermal growth factor and insulin had only a small effect on induction of Na+,K+-ATPase. A concentration of basic fibroblast growth factor three times higher than that of NGF showed a similar potency to NGF. The molecular form of the enzyme was judged as only the alpha form in both the untreated and the NGF-treated cells by a simple pattern of low-affinity interaction with cardiotonic steroids: inhibition of enzyme activity by strophanthidin (Ki approximately 1 mM) and inhibition of Rb+ uptake by ouabain (Ki approximately 100 microM). As a consequence, during differentiation of PC12h cells to neuron-like cells, NGF increases the alpha form of Na+,K+-ATPase, but does not induce the alpha(+) form of the enzyme, which has a high sensitivity for cardiotonic steroid and is a characteristic form in neurons.
D000310:Adrenal Gland Neoplasms / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D004790:Enzyme Induction; D006133:Growth Substances / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010673:Pheochromocytoma / Q000201:enzymology* / Q000473:pathology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013327:Strophanthidin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D007473:Ion Channels; D009414:Nerve Growth Factors; D013327:Strophanthidin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D011188:Potassium