دورية أكاديمية
An assessment of the transport mechanism and intraneuronal stability of L-carnosine.
| العنوان: | An assessment of the transport mechanism and intraneuronal stability of L-carnosine. |
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| المؤلفون: | Lopachev AV; Research Center of Neurology, 125367, Moscow, Russian Federation. lopachev@neurology.ru., Abaimov DA; Research Center of Neurology, 125367, Moscow, Russian Federation., Filimonov IS; All-Russian Research Institute for Optical and Physical Measurements, 119361, Moscow, Russian Federation., Kulichenkova KN; Research Center of Neurology, 125367, Moscow, Russian Federation., Fedorova TN; Research Center of Neurology, 125367, Moscow, Russian Federation. |
| المصدر: | Amino acids [Amino Acids] 2022 Aug; Vol. 54 (8), pp. 1115-1122. Date of Electronic Publication: 2021 Oct 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer-Verlag Country of Publication: Austria NLM ID: 9200312 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1438-2199 (Electronic) Linking ISSN: 09394451 NLM ISO Abbreviation: Amino Acids Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Wien ; New York : Springer-Verlag, c1991- |
| مواضيع طبية MeSH: | Carnosine*/metabolism , Carnosine*/pharmacology , Symporters*/metabolism, Animals ; Biological Transport, Active ; Choroid Plexus/metabolism ; Membrane Transport Proteins/metabolism ; Rats |
| مستخلص: | L-Carnosine (β-alanyl-L-histidine) is a well-known antioxidant and neuroprotector in various models on animals and cell cultures. However, while there is a plethora of data demonstrating its efficiency as a neuroprotector, there is a distinct lack of data regarding the mechanism of its take up by neurons. According to literature, cultures of rat astrocytes, SKPT cells and rat choroid plexus epithelial cells take up carnosine via the H + -coupled PEPT2 membrane transporter. We've assessed the effectiveness and mechanism of carnosine transport, and its stability in primary rat cortical culture neurons. We demonstrated that neurons take up carnosine via active transport with Km = 119 μM and a maximum velocity of 0.289 nmol/mg (prot)/min. Passive transport speed constituted 0.21∙10 -4 nmol/mg (prot)/min (with 119 μM concentration in the medium)-significantly less than active transport speed. However, carnosine concentrations over 12.5 mM led to passive transport speed becoming greater than active transport speed. Using PEPT2 inhibitor zofenopril, we demonstrated that PEPT2-dependent transport is one of the main modes of carnosine take up by neurons. Our experiments demonstrated that incubation with carnosine does not affect PEPT2 amount present in culture. At the same time, after removing carnosine from the medium, its elimination speed by culture cells reached 0.035 nmol/mg (prot)/min, which led to a decrease in carnosine quantity to control levels in culture within 1 h. Thus, carnosine is taken up by neurons with an effectiveness comparable to that of other PEPT2 substrates, but its elimination rate suggests that for effective use as a neuroprotector it's necessary to either maintain a high concentration in brain tissue, or increase the effectiveness of glial cell synthesis of endogenous carnosine and its shuttling into neurons, or use more stable chemical modifications of carnosine. (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.) |
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| فهرسة مساهمة: | Keywords: Carnosine; Neuron; PEPT2; Take up; Transport efficiency; Transport kinetics |
| المشرفين على المادة: | 0 (Membrane Transport Proteins) 0 (Symporters) 8HO6PVN24W (Carnosine) |
| تواريخ الأحداث: | Date Created: 20211025 Date Completed: 20220812 Latest Revision: 20220812 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1007/s00726-021-03094-5 |
| PMID: | 34694500 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1438-2199 |
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| DOI: | 10.1007/s00726-021-03094-5 |