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ウマが人の行動を認識するのは「声」と「表情」の関連から (NHK)

移動の足などとして数千年前から家畜化が進んだウマは、人の声と表情の2つを関連づけて人の行動を認識していることが北海道大学などの実験でわかりました。身近な動物が人...

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3,4-Dihydroxyphenylacetaldehyde- (DOPAL)-induced protein modifications and their mitigation by N-acetylcysteine.

著者 Jinsmaa Y , Sharabi Y , Sullivan P , Isonaka R , Goldstein DS
J Pharmacol Exp Ther.2018 Apr 26 ; ():.
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The catecholaldehyde hypothesis posits that 3,4-dihydroxyphenylacetaldehyde (DOPAL), an obligate intermediary metabolite of dopamine (DA), is an autotoxin that challenges neuronal homeostasis in catecholaminergic neurons. DOPAL toxicity may involve protein modifications, such as oligomerization of alpha-synuclein (AS). Potential interactions between DOPAL and other proteins related to catecholaminergic neurodegeneration, however, have not been systemically explored. This study examined DOPAL-induced protein-quinone adduct formation ("quinonization") and protein oligomerization, ubiquitination, and aggregation in cultured MO3.13 human oligodendrocytes and PC12 rat pheochromocytoma cells and in test tube experiments. Using near infrared fluorescence spectroscopy we detected spontaneous DOPAL oxidation to DOPAL-quinone, DOPAL-induced quinonization of intracellular proteins in both cell lines and DOPAL-induced quinonization of several proteins related to catecholaminergic neurodegeneration, including AS, the type 2 vesicular monoamine transporter, glucocerebrosidase, ubiquitin, and L-aromatic-amino-acid decarboxylase (LAAAD). DOPAL also oligomerized AS, ubiquitin, and LAAAD, inactivated LAAAD (IC50=54 uM), evoked substantial intracellular protein ubiquitination, and aggregated intracellular AS. Remarkably, N-acetylcysteine, which decreases DOPAL-quinone formation, attenuated or prevented all these protein modifications and functional changes. The results fit with the proposal that treatments based on decreasing the formation and oxidation of DOPAL may slow or prevent catecholaminergic neurodegeneration. .
PMID: 29700232 [PubMed - as supplied by publisher]
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