Magnetic resonance studies on the mechanism of the enzymic β-hydroxylation of 3,4-dihydroxyphenylethylamine

Blumberg, W. E.; Goldstein, Menek; Lauber, E.; Peisach, Jack

doi:10.1016/s0926-6593(65)80025-x

Cited by 58 publications

(13 citation statements)

References 8 publications

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“…The SNR of LC is not significantly different in DBH(−/−) (47.9 ± 4.4, n = 5) compared with DBH(+/−) mice (46.3 ± 2.6, n = 5). This indicates that neither the presence of dopamine β-hydroxylase nor its binding to Cu 2+ ions (Blumberg et al 1965) is the source of the high MRI signal intensity.…”

Section: Resultsmentioning

confidence: 99%

Magnetic resonance imaging of noradrenergic neurons

et al. 2019

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Noradrenaline is a neurotransmitter involved in general arousal, selective attention, memory, inflammation, and neurodegeneration. The purpose of this work was to delineate noradrenergic neurons in vivo by T 1 -weighted MRI with magnetization transfer (MT). In the brainstem of human and mice, MRI identified the locus coeruleus, dorsal motor vagus nucleus, and nucleus tractus solitarius. Given (1) the long T 1 and low magnetization transfer ratio for the noradrenergic cell groups compared to other gray matter, (2) significant correlation between MT MRI signal intensity and proton density, and (3) no correlation between magnetization transfer ratio (or R 1 ) and iron, copper, or manganese in human brain, the high MRI signal of the noradrenergic neurons must be attributed to abundant water protons interacting with any T 1 -shortening paramagnetic ions in active cells rather than to specific T 1 -shortening molecules. The absence of a high MRI signal from the locus coeruleus of Ear2(−/−) mice lacking noradrenergic neurons confirms that cell bodies of noradrenergic neurons are the source of the bright MRI appearance. The observation of this high signal in DBH(−/−) mice, in 3-week-old mice, and in mice under hyperoxia/hypercapnia/hypoxia together with the general absence of neuromelanin (NM) in noradrenergic neurons of young rodents further excludes that it is due to NM, dopamine β-hydroxylase, their binding to paramagnetic ions, blood inflow, or hemoglobin. Instead, these findings indicate a high density of water protons whose T 1 is shortened by paramagnetic ions as the relevant source of the high MRI signal. In the brain of APP/PS1/Ear2(−/−) mice, a transgenic model of Alzheimer’s disease, MRI detected noradrenergic neuron loss in the locus coeruleus. Proton magnetic resonance spectroscopy revealed that a 60–75% reduction of noradrenaline is responsible for a reduction of N -acetylaspartate and glutamate in the hippocampus as well as for a shortening of the water proton T 2 in the frontal cortex. These results suggest that a concurrent shortage of noradrenaline in Alzheimer’s disease accelerates pathologic processes such as inflammation and neuron loss. Electronic supplementary material The online version of this article (10.1007/s00429-019-01858-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Magnetic resonance imaging of noradrenergic neurons

et al. 2019

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“…In view of the fact that paramagnetic metal ions can in general produce magnetic field dependence in the T1 values of solvent protons however, it is necessary to consider whether the observed T1 dispersion could be a paramagnetic effect without invoking assumptions concerning the structural organization of the granules. Relaxation enhancements produced by dopamine/3-hydroxylase have been studied previously [12] however and are found to be far too small to account for the T1 dispersion.…”

Section: Effects Of Paramagnetic Metal Ionsmentioning

confidence: 92%

Molecular mobilities in chromaffin granules magnetic field dependence of proton T1 relaxation times

Sharp¹,

Sen²

1978

Biochimica et Biophysica Acta (BBA) - General Subjects

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The magnetic field dependence of the NMR spin-lattice relaxation time of water protons in intact bovine chromaffin vesicles has been studied over the range 1.00-23.49 kG. The T~ relaxation time shows a dispersion at field values near 20 kG. The observed proton resonance arises mainly from solvent protons (~H20), but the relaxation rate, which is a weighted average over all sites with which the solvent protons rapidly exchange (i.e., NH and OH protons), is dominated by exchangeable protons in the most slowly moving soluble component. The field dependence of the T1 dispersion demonstrates the existence of a site of exchangeable protons for which Tr = 1.9 + 0.5 ns at 3°C. This site is assigned to ATP and cationic groups to which its phosphate esters are complexed, since previously measured correlation times of epinephrine and the chromogranin backbone are nearly an order of magnitude too short to explain the T~ dispersion. Quantitative estimates of the relative numbers of exchangeable protons on the different soluble components support this interpretation. The temperature dependence of T1 of the peak due to exchangeable protons has also been measured over a temperature range-3 to 25°C. T~ lengthens by about 30% over this range and exhibits'no discontinuous behavior, as would be expected if a gel transition or structural alterations in the storage complex occurred. T~ lengthens by less than 10% in chromaffin granule pastes that have been maintained at 25°C for 24 h, indicating considerable thermal stability in the storage complex. Possible effects on the solvent T~ due to paramagnetic ions have been considered with the conclusion that they are probably negligible or of minor significance.

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“…EPR spectra of resting DbM were also consistent with two Cu(ii) sites per active site with little residual Cu(i). [31][32][33] The a-carbon of the terminal glycine is oxidized as the glycine-extended peptide is converted to glyoxylate. A redox role for the two PHM-bound copper atoms seemed likely: the two DbM-bound copper atoms underwent redox chemistry during catalysis 33,34 and each PHM turnover required the input of two electrons from two one-electron oxidation reactions of ascorbate to the semidehydroascorbate radical.…”

Section: Oxidation/reduction At the Phm-bound Copper Atomsmentioning

confidence: 99%