Effect of the 1-methyl-4-phenylpyridinium ion on phosphorylation of tyrosine hydroxylase in rat pheochromocytoma PC12h cells. 1988

K Kiuchi, and M Hagiwara, and H Hidaka, and T Nagatsu
Department of Biochemistry, Nagoya University School of Medicine, Japan.

Effects of the 1-methyl-4-phenylpyridinium ion (MPP+) on DOPA formation and phosphorylation of tyrosine hydroxylase (TH) of rat pheochromocytoma PC12h cells were examined after the cells were cultured with MPP+. DOPA formed from endogenous tyrosine in PC12h cells after a 3-day culture with 100 microM MPP+ was decreased to less than 50% as compared to that in the control cells cultured without MPP+. Kinetical study showed that two apparent forms of TH with different Km existed in the cells cultured with 100 microM MPP+ but one form in that of control. Incorporation of radioactive phosphate into TH molecule was also reduced to 50% of its control value following a 3-day exposure to 100 microM MPP+. These results suggest that MPP+ acutely inhibits the phosphorylation of TH to decrease cellular DOPA formation.

UI MeSH Term Description Entries
D010673 Pheochromocytoma A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of EPINEPHRINE and NOREPINEPHRINE, is HYPERTENSION, which may be persistent or intermittent. During severe attacks, there may be HEADACHE; SWEATING, palpitation, apprehension, TREMOR; PALLOR or FLUSHING of the face, NAUSEA and VOMITING, pain in the CHEST and ABDOMEN, and paresthesias of the extremities. The incidence of malignancy is as low as 5% but the pathologic distinction between benign and malignant pheochromocytomas is not clear. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1298) Pheochromocytoma, Extra-Adrenal,Extra-Adrenal Pheochromocytoma,Extra-Adrenal Pheochromocytomas,Pheochromocytoma, Extra Adrenal,Pheochromocytomas,Pheochromocytomas, Extra-Adrenal
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011726 Pyridinium Compounds Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N. Compounds, Pyridinium
D004295 Dihydroxyphenylalanine A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific. Dopa,3,4-Dihydroxyphenylalanine,3-Hydroxy-DL-tyrosine,Dihydroxyphenylalanine Hydrochloride, (2:1),beta-Hydroxytyrosine,3 Hydroxy DL tyrosine,3,4 Dihydroxyphenylalanine,beta Hydroxytyrosine
D000310 Adrenal Gland Neoplasms Tumors or cancer of the ADRENAL GLANDS. Adrenal Cancer,Adrenal Gland Cancer,Adrenal Neoplasm,Cancer of the Adrenal Gland,Neoplasms, Adrenal Gland,Adrenal Cancers,Adrenal Gland Cancers,Adrenal Gland Neoplasm,Adrenal Neoplasms,Cancer, Adrenal,Cancer, Adrenal Gland,Cancers, Adrenal,Cancers, Adrenal Gland,Neoplasm, Adrenal,Neoplasm, Adrenal Gland,Neoplasms, Adrenal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014446 Tyrosine 3-Monooxygenase An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2. Tyrosine Hydroxylase,3-Monooxygenase, Tyrosine,Hydroxylase, Tyrosine,Tyrosine 3 Monooxygenase
D015655 1-Methyl-4-phenylpyridinium An active neurotoxic metabolite of 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE. The compound reduces dopamine levels, inhibits the biosynthesis of catecholamines, depletes cardiac norepinephrine and inactivates tyrosine hydroxylase. These and other toxic effects lead to cessation of oxidative phosphorylation, ATP depletion, and cell death. The compound, which is related to PARAQUAT, has also been used as an herbicide. Cyperquat,1-Methyl-4-phenylpyridine,1-Methyl-4-phenylpyridinium Chloride,1-Methyl-4-phenylpyridinium Ion,N-Methyl-4-phenylpyridine,N-Methyl-4-phenylpyridinium,1 Methyl 4 phenylpyridine,1 Methyl 4 phenylpyridinium,1 Methyl 4 phenylpyridinium Chloride,1 Methyl 4 phenylpyridinium Ion,N Methyl 4 phenylpyridine
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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