Biomedical subjects
M Moeller
Publications and source records attributed to M Moeller.
Cyclic adenosine 3',5'-monophosphate and glucose stimulate thyroxine 5'-deiodinase type II in cultured mouse neuroblastoma cells.
Nutrient modulation increases mouse neuroblastoma (NB) T4-5'-deiodinase II (T4-5'-D II) activity. Carbohydrates are more potent than either amino acids or glycerol as nutrient sources. Glucose rapidly (2 to 4 hours) enhances NB enzyme activity and the response is dependent on new protein synthesis. The present study was performed to further characterize this glucose effect and explore its relationship to the cyclic adenosine monophosphate (cAMP) system in these cells. NB T4-5'-D II activity reached a maximum level (sixfold) in response to glucose (10 mmol/L) at 16 hours and thereafter remained constant up to 22 hours before reverting back to basal level between 24 and 30 hours. This pattern of response allowed the performance of detailed studies on maximum glucose activated NB T4-5'-D II under transient equilibrium conditions during the 16- to 22-hour period. Addition of dibutyryl cAMP (dbcAMP) (1 mmol/L) at this stage significantly increased enzyme activity (twofold at 2 hours and fourfold at 4 and 6 hours) compared with glucose alone. There was an additive response to dbcAMP under these maximum glucose-activated conditions. Nonactivated NB T4-5'-D II showed a twofold response to dbcAMP (1 mmol/L) at 4 hours in a glucose-free medium. Under these conditions, glucose (10 mmol/L) also increased enzyme activity twofold. Combined studies with dbcAMP and glucose increased enzyme activity fourfold at 4 hours. Subsequent studies were performed with forskolin (10 mumol/L) and cholera toxin (1 nmol/L), modulators of endogenous cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Reverse T3 and modulators of the calcium messenger system rapidly decrease T4-5'-deiodinase II activity in cultured mouse neuroblastoma cells.
Neural T3 neogenesis is modulated by the enzyme T4-5'-deiodinase type II (T4-5'-DII). Hypothyroidism increases the activity of rat pituitary and cerebral cortex enzyme activity. Mouse neuroblastoma cells (NB41A3) incubated in thyroid hormone deficient medium also show a significant increase in T4-5'-DII activity. This response is rapidly (less than 30 minutes) reversed by reverse T3 (rT3) suggesting a mechanism independent of nuclear T3 receptor binding or new protein synthesis. This report details a series of studies performed to elucidate the nature of this rT3 effect. Confluent neuroblastoma cell culture preparations maintained in hypothyroid medium showed a 2-3 fold increase in T4-5'-DII activity compared to preparations in standard medium (p less than 0.001). RT3 (1-50 nM), the calcium ionophore A23187 (0.3-1.5 microM) and the phorbol ester TPA (0.1-1.0 microM) reversed the effect of thyroid hormone deficient medium on enzyme activity (p less than 0.001). Each agent showed a similar time course with maximal effect occurring between 15-30 minutes post medium supplementation. The suppressive effect of A23187 (1.5 microM) and TPA (0.5 microM) on enzyme activity was not additive. In addition, the combination o of rT3 (50 nM) and A23187 (1.5 nM) did not decrease enzyme activity compared to each agent alone. In contrast, the combined addition of rT3 (50 nM) and TPA (0.5 microM) did have an additive effect on neuroblastoma T4-5'-DII activity. A similar pattern of response was found, when the effects of these agents were analyzed on T4-5'-DII activity in neuroblastoma cells incubated in N-FSC.(ABSTRACT TRUNCATED AT 250 WORDS)