Кокаин-амфетамин-регулируемый транскрипт – многообещающий омиксный прорыв в эндокринологии <span class="so-article-trans-title" dir="auto"> Translated title: Cocaine-amphetamine regulated transcript (CART) — promising omics breakthrough in the endocrinology </span>

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Abstract

ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Со дня открытия кокаин-амфетамин-регулируемого транскрипта (КАРТ) прошло более четверти века. При этом данный транскрипт незаслуженно остается «в тени», несмотря на проявляемый в последние годы неподдельный интерес со стороны ученого сообщества.

ЦЕЛЬ

ЦЕЛЬ. Оценить «исторические вехи» и перспективы изучения КАРТ в медицине.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. Поиск литературы проводили в отечественных (eLibrary, CyberLeninka.ru) и международных (PubMed, Cochrane Library) базах данных на русском и английском языках. Приоритетным являлся свободный доступ к полному тексту статей. Выбор источников был приоритетен периодом с 2019 по 2021 гг. Однако с учетом недостаточной изученности выбранной темы выбор источников датировался с 1989 г. Работа выполнена в рамках Государственного задания «Центральные и периферические патофизиологические механизмы развития болезней жировой ткани с учетом клинических и гормональных характеристик», 2020–2022 гг.

РЕЗУЛЬТАТЫ И ВЫВОДЫ

РЕЗУЛЬТАТЫ И ВЫВОДЫ. Для того чтобы здравоохранение научилось более эффективно «держать удар» перед неуклонно растущей распространенностью метаболических заболеваний (ожирение, сахарный диабет и т.п.) в мире, жизненно важно открывать и изучать новые геномные, протеомные и метаболомные паттерны. В частности, одним из таких паттернов могут стать исследования, посвященные эффективности изучения возможности применения КАРТ для лечения метаболических заболеваний с позиций доказательной медицины. Чем раньше произойдет консолидация усилий клинических врачей, экспертов в области фундаментальной науки, в том числе для изучения молекулярных механизмов функционирования гипоталамо-гипофизарной системы, тем быстрее приблизится долгожданная смена парадигмы клинико-синдромальной медицины на парадигму трансляционно-персонализированной.

Translated abstract

BACKGROUND

BACKGROUND: The cocaine-amphetamine regulated transcript has been discovered long time ago (circa over 25 years ago) but still stays not enough investigated. Just during last five years scientist’s society started providing interest to the genomic, proteomic and metabolic essence of the cocaine-amphetamine regulated transcript.

AIM

AIM: The evaluation of historical pathway and perspectives of the cocaine-amphetamine regulated transcript medical investigations.

MATERIALS AND METHODS

MATERIALS AND METHODS: The literature search has been provided via Russian (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases and among articles on Russian and English languages. The main criteria for article selection was free access and 2019–2021 years of publishing. Although the introduction is based on the articles published in 1989. The present article was created according to the federal project «Central and peripheral pathophysiological mechanisms of adipose tissue diseases and their clinical and hormonal manifestations» (2020–2022)

RESULTS AND CONCLUISON

RESULTS AND CONCLUISON: It is necessary to keep on investigating genomic, proteomic and metabolomic markers because they contain important clues for successful resistance against human diseases. The 21st century is the era of transformation from simple clinical medicine to personalized science. For example, researches in the area of cocaine-amphetamine regulated transcript may result in invention of genetic medicine against dangerous metabolic diseases.

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Most cited references 20

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Hypothalamic CART is a new anorectic peptide regulated by leptin.

N Vrang, L Thim, U Ribel … (1998)

The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.

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Record: found
Abstract: found
Article: not found

PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine.

J. Douglass, AA McKinzie, P Couceyro (1995)

Neuronal plasticity associated with both short- and long-term administration of psychomotor stimulants involves alterations in specific patterns of gene expression. In order to screen for brain region specific mRNAs which are transcriptionally regulated by acute cocaine and amphetamine, PCR differential display was employed. This approach identified a previously uncharacterized mRNA whose relative levels in the striatum are induced four- to fivefold by acute psychomotor stimulant administration. Isolation and characterization of corresponding cDNA clones resulted in complete nucleotide sequence analysis, including prediction of the encoded protein product. Alternate polyA site utilization in the predicted 3' noncoding region results in the appearance of an RNA doublet, approximately 700 and 900 bases in length, following Northern analysis. A presumed alternate splicing event further generates diversity within the transcripts, and results in the presence or absence of an in-frame 39 base insert within the putative protein coding region. As a result, the predicted translation products are either 129 or 116 amino acids in length. A common hydrophobic leader sequence at the amino terminus is present within each predicted polypeptide, suggesting that the protein product is targeted for entry into the secretory pathway. Basal expression of the RNA doublet is limited to neuroendocrine tissues, further implying that the protein product plays a functional role in both neuronal and endocrine tissues.

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Record: found
Abstract: found
Article: not found

Microbiota-modulated CART+ enteric neurons autonomously regulate blood glucose

Paul Muller, Fanny Matheis, Marc Schneeberger … (2020)

The gut microbiota affects tissue physiology, metabolism, and function of both the immune and nervous systems. We found that intrinsic enteric-associated neurons (iEAN) in mice are functionally adapted to the intestinal segment they occupy; ileal and colonic neurons are more responsive to microbial colonization than duodenal neurons. Specifically, a microbially-responsive subset of viscerofugal CART+ neurons, enriched in the ileum and colon, modulated feeding and glucose metabolism. These CART+ neurons send axons to the prevertebral ganglia and are poly-synaptically connected to the liver and pancreas. Microbiota depletion led to NLRP6– and Caspase 11-dependent loss of CART+ neurons, and impaired glucose regulation. Hence, iEAN subsets appear to be capable of regulating blood glucose levels independently from the central nervous system.

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Author and article information

Contributors

Р. К. Михеев

Т. И. Романцова

Е. А. Трошина

О. Р. Григорян

Е. Н. Андреева

Е. В. Шереметьева

Ю. С. Абсатарова

Н. Г. Мокрышева

Journal

Journal ID (nlm-ta): Probl Endokrinol (Mosk)

Journal ID (iso-abbrev): Probl Endokrinol (Mosk)

Journal ID (publisher-id): problendo

Title: Problems of Endocrinology

Publisher: Endocrinology Research Centre

ISSN (Print): 0375-9660

ISSN (Electronic): 2308-1430

Publication date Collection: 2022

Publication date (Electronic): 25 January 2022

Volume: 68

Issue: 2

Pages: 4-8

Affiliations

[-1]Национальный медицинский исследовательский центр эндокринологии

[-2]Первый московский государственный медицинский университет им. И.М. Сеченова (Сеченовский университет)

[-3]Национальный медицинский исследовательский центр эндокринологии

[-4]Национальный медицинский исследовательский центр эндокринологии

[-5]Национальный медицинский исследовательский центр эндокринологии

[-6]Национальный медицинский исследовательский центр эндокринологии

[-7]Национальный медицинский исследовательский центр эндокринологии

[-8]Национальный медицинский исследовательский центр эндокринологии

Article

DOI: 10.14341/probl12872

PMC ID: 9112847

PubMed ID: 35488751

SO-VID: 68b3030d-ab6b-471a-bfbb-db6726004a2c

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This work is licensed under a Creative Commons Attribution 4.0 License.

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Кокаин-амфетамин-регулируемый транскрипт – многообещающий омиксный прорыв в эндокринологии Translated title: Cocaine-amphetamine regulated transcript (CART) — promising omics breakthrough in the endocrinology

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