A novel enzyme enantio-selectively synthesizes (R)salsolinol, a precursor of a dopaminergic neurotoxin, N-methyl(R)salsolinol

Naoi, Makoto; Maruyama, Wakako; Dostert, P.; Kohda, Kohfuku; Kaiya, Toyo

doi:10.1016/0304-3940(96)12807-x

Cited by 124 publications

(61 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This catechol isoquinoline may be synthesized directly from DA and acetaldehyde or indirectly, forming salsolinol-1-carboxylic acid and further to salsolinol (Naoi et al 1996(Naoi et al , 2002. Although not all enzymes of an indirect pathway of salsolinol synthesis are known, this compound and its metabolites can be detected in many areas of the brain that are also rich in DA (Toth et al 2001, Naoi et al 2002.…”

Section: Discussionmentioning

confidence: 99%

“…As reported by Naoi et al (1996Naoi et al ( , 2002, salsolinol can be synthesized from dopamine (DA) and acetaldehyde or alternatively, from DA and pyruvic acid by forming an intermediate metabolite, salsolinol-1-carboxylic acid. This DA-originated compound, which is well known from its involvement in the progression of a disease characterized by dysfunctional dopaminergic neurons (Moser et al 1995, Antkiewicz-Michaluk 2002, was found to be present in neuro-intermediate lobe (NIL) as well as median eminence (ME) extracts of male, intact and ovariectomized female rats (Toth et al 2001).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of salsolinol in the mediobasal hypothalamus of lactating ewes and its relation to suckling-induced prolactin and GH release

Misztal

Górski²,

Tomaszewska-Zaremba³

et al. 2008

Journal of Endocrinology

View full text Add to dashboard Cite

The push-pull perfusions of the infundibular nucleus-median eminence (IN/ME) were made in lactating ewes (nZ7) twice, to identify dopamine (DA)-derived salsolinol and the changes in its extracellular concentration in response to suckling. The perfusate collecting period in every ewe consisted of control non-suckling period, 1000-1230 h (five perfusates), and suckling period, 1230-1500 h (next five perfusates). Simultaneously, blood samples were collected from 1000 to 1500 h at 10-min intervals. The perfusate concentrations of salsolinol and DA were measured by HPLC, and plasma prolactin and GH concentrations were assayed by the RIA. Mean concentrations of salsolinol in perfusates collected from the anterior and posterior parts of the IN/ME (according to post-mortem localization of a perfusion site) increased significantly (P!0 . 05 and P!0 . 001 respectively) during the suckling period, when compared with those noted during the non-suckling period. While no DA was found in the anterior part, only vestigial amounts of DA were found in a few perfusates collected from the posterior part. Salsolinol was not detected in the IN/ME of ewes 10 weeks after weaning (seasonal anoestrus). Mean plasma prolactin and GH concentrations during suckling were significantly (P!0 . 001) higher than those noted during the non-suckling period. In conclusion, our current study reveals that salsolinol is present in the IN/ME of lactating ewes and that its extracellular concentration increases during suckling. Moreover, it supports the role of salsolinol as a neurotransmitter involved in the regulatory process of prolactin secretion at least during lactation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of salsolinol in the mediobasal hypothalamus of lactating ewes and its relation to suckling-induced prolactin and GH release

Misztal

Górski²,

Tomaszewska-Zaremba³

et al. 2008

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…19 Actually, an enzyme, which enantioselectively synthesized (R)-Sal, has been isolated from rat brain. 20 Studies on the stereoselective neurotoxicity of TIQs have promoted the development of analytical methods for the determination of TIQ enantiomers. Several HPLC procedures [21][22][23] and a capillary electrochromatographic (CEC) method 24 were reported for the separation of Sal and N-methyl-Sal enantiomers.…”

Section: Introductionmentioning

confidence: 99%

Chiral CE Separation of Dopamine-Derived Neurotoxins

et al. 2005

View full text Add to dashboard Cite

An enantiomeric separation of dopamine-derived neurotoxins by capillary electrophoresis has been developed. Tetrahydroisoquinoline (TIQ), dopamine (DA), (R/S)-1-benzyl-TIQ (BTIQ), (R/S)-6,7-dihydroxy-1-methyl-TIQ (salsolinol, Sal), and (R/S)-6,7-dihydroxy-1, 2-dimethyl-TIQ (N-methyl-salsolinol, NMSal) were studied as model compounds. The CE running buffer (50 mM phosphate buffer at pH 3.0) contained 1.5 M urea and 12 mM β-CD as a chiral selector. During separation, the (R)-enantiomers formed more stable inclusion complexes with β-CD, and thus had a longer migration time than their optical antipodes. It was noticed that the recovery rates of these TIQ derivatives were very poor (< 15%) during protein precipitation, a procedure widely used for cleaning up biological samples. The recovery was significantly improved by pre-mixing the sample with a surfactant (e.g., sodium hexanesulfonate or Triton X-100) to reduce the co-precipitation. The present method in combination with electrospray ionization tandem mass spectrometry (ESI-MS/MS) was applied to study samples obtained from in vitro incubation of two catecholamines, dopamine and epinine, with aldehydes forming neurotoxins including (S)-and (R)-NMSal enantiomers. The later is known to induce Parkinsonism in rats.

show abstract

“…The cytosol and mitochondria fraction were prepared from the cells treated with 10 lg/mL NM, DAM, or 100 lM DA for 2 h, according to Musderman et al (2004). HPLC with electrochemical detection was used to identify and quantify GSH in melanin-treated mitochondria, using conditions reported previously (Naoi et al 1996). GSH was identified and quantified by comparison with GSH standard.…”

Section: Assay For Activities Of Caspasementioning

confidence: 99%

Neuromelanin selectively induces apoptosis in dopaminergic SH‐SY5Y cells by deglutathionylation in mitochondria: involvement of the protein and melanin component

Naoi¹,

Maruyama

Yi³

et al. 2008

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

Parkinson’s disease (PD) is characterized by selective depletion of nigral dopamine (DA) neurons containing neuromelanin (NM), suggesting the involvement of NM in the pathogenesis. This study reports induction of apoptosis by NM in SH‐SY5Y cells, whereas protease‐K‐treated NM, synthesized DA‐ and cysteinyl dopamine melanin showed much less cytotoxicity. Cell death was mediated by mitochondria‐mediated apoptotic pathway, namely collapse of mitochondrial membrane potential, release of cytochrome c, and activation of caspase 3, but Bcl‐2 over‐expression did not suppress apoptosis. NM increased sulfhydryl content in mitochondria, and a major part of it was identified as GSH, whereas dopamine melanin significantly reduced sulfhydryl levels. Western blot analysis for protein‐bound GSH demonstrated that only NM reduced S‐glutathionylated proteins in mitochondria and dissociated macromolecular structure of complex I. Reactive oxygen and nitrogen species were required for the deglutathionylation by NM, which antioxidants reduced significantly with prevention of apoptosis. These results suggest that NM may be related to cell death of DA neurons in PD and aging through regulation of mitochondrial redox state and S‐glutathionylation, for which NM‐associated protein is absolutely required. The novel function of NM is discussed in relation to the pathogenesis of PD.

show abstract

A novel enzyme enantio-selectively synthesizes (R)salsolinol, a precursor of a dopaminergic neurotoxin, N-methyl(R)salsolinol

Cited by 124 publications

References 17 publications

Identification of salsolinol in the mediobasal hypothalamus of lactating ewes and its relation to suckling-induced prolactin and GH release

Identification of salsolinol in the mediobasal hypothalamus of lactating ewes and its relation to suckling-induced prolactin and GH release

Chiral CE Separation of Dopamine-Derived Neurotoxins

Neuromelanin selectively induces apoptosis in dopaminergic SH‐SY5Y cells by deglutathionylation in mitochondria: involvement of the protein and melanin component

Contact Info

Product

Resources

About