Mass fragmentography of 5-hydroxytryptophol and 5-methoxytryptophol in human cerebrospinal fluid

Curtius, Hans−Christoph; Wolfensberger, M.; Redweik, U.; Leimbacher, Walter; Maibach, R.A.; Isler, W

doi:10.1016/s0021-9673(00)99981-3

Cited by 24 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6-OHDA can be formed from dopamine by nonenzymatic hydroxylation in the presence of Fe 2+ and H 2 O 2 (19). Endogenous 6-OHDA was detected in the brain and urine samples of patients suffering from PD (20)(21)(22), suggesting that this compound is involved in the pathogenesis of PD. The cellular and molecular mechanisms by which 6-OHDA induces neuronal loss, however, are not clear.…”

mentioning

confidence: 99%

Expression of Concern: Glycogen synthase kinase 3β (GSK3β) mediates 6‐ hydroxydopamine‐induced neuronal death

et al. 2004

View full text Add to dashboard Cite

The causes of sporadic Parkinson's disease (PD) are poorly understood. 6-Hydroxydopamine (6-OHDA), a PD mimetic, is widely used to model this neurodegenerative disorder in vitro and in vivo; however, the underlying mechanisms remain incompletely elucidated. We demonstrate here that 6-OHDA evoked endoplasmic reticulum (ER) stress, which was characterized by an up-regulation in the expression of GRP78 and GADD153 (Chop), cleavage of procaspase-12, and phosphorylation of eukaryotic initiation factor-2 alpha in a human dopaminergic neuronal cell line (SH-SY5Y) and cultured rat cerebellar granule neurons (CGNs). Glycogen synthase kinase-3 beta (GSK3beta) responds to ER stress, and its activity is regulated by phosphorylation. 6-OHDA significantly inhibited phosphorylation of GSK3beta at Ser9, whereas it induced hyperphosphorylation of Tyr216 with little effect on GSK3beta expression in SH-SY5Y cells and PC12 cells (a rat dopamine cell line), as well as CGNs. Furthermore, 6-OHDA decreased the expression of cyclin D1, a substrate of GSK3beta, and dephosphorylated Akt, the upstream signaling component of GSK3beta. Protein phosphatase 2A (PP2A), an ER stress-responsive phosphatase, was involved in 6-OHDA-induced GSK3beta dephosphorylation (Ser9). Blocking GSK3beta activity by selective inhibitors (lithium, TDZD-8, and L803-mts) prevented 6-OHDA-induced cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), DNA fragmentations and cell death. With a tetracycline (Tet)-controlled TrkB inducible system, we demonstrated that activation of TrkB in SH-SY5Y cells alleviated 6-OHDA-induced GSK3beta dephosphorylation (Ser9) and ameliorated 6-OHDA neurotoxicity. TrkB activation also protected CGNs against 6-OHDA-induced damage. Although antioxidants also offered neuroprotection, they had little effect on 6-OHDA-induced GSK3beta activation. These results suggest that GSK3beta is a critical intermediate in pro-apoptotic signaling cascades that are associated with neurodegenerative diseases, thus providing a potential target site amenable to pharmacological intervention.

show abstract

mentioning

confidence: 99%

Expression of Concern: Glycogen synthase kinase 3β (GSK3β) mediates 6‐ hydroxydopamine‐induced neuronal death

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The serotonin metabolite 5-hydroxytryptophol (5-HTOL) occurs in human CSF (Curtius et al, 1975;Takahashi et al, 1978), in rat tissues and fluids (Cheifetz and Warsh, 1980), and in mouse brain (Diggory et al, 1979). Also, CSF 5-HTOL in humans increases during ethanol intoxication and disulfiram therapy, so that alcoholics have higher levels than healthy volunteers, even after abstinence from ethanol for several weeks (Beck et al, 1980a,h;1982).…”

mentioning

confidence: 99%

5‐Hydroxytryptophol in Human Cerebrospinal Fluid: Conjugation, Concentration Gradient, Relationship to 5‐Hydroxyindoleacetic Acid, and Influence of Hereditary Factors

Beck¹,

Borg²,

Edman³

et al. 1984

Journal of Neurochemistry

View full text Add to dashboard Cite

The serotonin metabolite 5-hydroxytryptophol was studied in human cerebrospinal fluid. A minor fraction (approximately 13%) was found in conjugated form from which it was liberated by treatment with sulphatase containing beta-glucuronidase activity. A concentration gradient of 5-hydroxytryptophol concentration was shown on lumbar tapping and the concentration in ventricular CSF was about 2.5 times higher than that in lumbar CSF. 5-Hydroxytryptophol and 5-hydroxyindoleacetic acid concentrations were significantly correlated in healthy, psychotic, and depressed subjects, but not in alcoholics. 5-Hydroxytryptophol concentrations in CSF of psychotic and depressed subjects were not different from those of healthy controls (4.22 pmol/ml +/- 0.15, SEM). In healthy subjects, hereditary factors seemed to have little influence on the CSF level of 5-hydroxytryptophol.

show abstract

“…In addition, synergistic effects of tryptophan and ethanol on sleep parameters have been reported in rats (Hill and Reyes, 1978). The structural similarity of tryptamine and tryptophol, together with their roles in sleep induction and the demonstration of endogenously formed 5-hydroxytryptophol in human cerebrospinal fluid (Curtius et al, 1975;Takahashi et al, 1978) and mouse brain (Diggory et al, 1979) seem to indicate a functional role as an endogenous hypnotic (Taborsky, 1971 ;Feldstein and Kucharski, 1971;Feldstein, 1973;Wilson et al, 1978).…”

Section: Discussionmentioning

confidence: 94%

Reduction in Brain Glucose Utilization Rate after Tryptophol (3‐Indole Ethanol) Treatment

Cornford¹,

Crane²,

Braun³

et al. 1981

Journal of Neurochemistry

View full text Add to dashboard Cite

3-Indole ethanol has been recently identified as the hypnotic agent in trypanosomal sleeping sickness, and because it is formed in vivo after ethanol or disulfiram treatment, is also associated with the study of alcoholism. When administered intraperitoneally to rats (250 mg/kg) tryptophol induced a sleep-like state that lasted less than an hour (no righting reflex was apparent 2 min after injection, but it returned at 11 min in bovine serum albumin solution, and 47 min in 40% ethanol solution). In ethanol solutions, tryptophol reduced brain cortical glucose utilization by 55% to the basal brain metabolic rate, and this effect lasted less than 1 h. Synergistic effects of tryptophol and ethanol were suggested by the observation that in albumin solution, tryptophol reduced brain glucose utilization by 35%, but a normal rate was not observed until 2 h postinjection.

show abstract

Mass fragmentography of 5-hydroxytryptophol and 5-methoxytryptophol in human cerebrospinal fluid

Cited by 24 publications

References 14 publications

Expression of Concern: Glycogen synthase kinase 3β (GSK3β) mediates 6‐ hydroxydopamine‐induced neuronal death

Expression of Concern: Glycogen synthase kinase 3β (GSK3β) mediates 6‐ hydroxydopamine‐induced neuronal death

5‐Hydroxytryptophol in Human Cerebrospinal Fluid: Conjugation, Concentration Gradient, Relationship to 5‐Hydroxyindoleacetic Acid, and Influence of Hereditary Factors

Reduction in Brain Glucose Utilization Rate after Tryptophol (3‐Indole Ethanol) Treatment

Contact Info

Product

Resources

About