Carnitine Traffic in Cells. Link With Cancer

Console, Lara; Scalise, Mariafrancesca; Mazza, Tiziano; Pochini, Lorena; Galluccio, Michele; Giangregorio, Nicola; Tonazzi, Annamaria; Indiveri, Cesare

doi:10.3389/fcell.2020.583850

Cited by 47 publications

(34 citation statements)

References 150 publications

(241 reference statements)

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“…In this altered metabolic condition, acyl-carnitines fail to reach the mitochondrial matrix with consequent strong impairment of the β-oxidation. This syndrome is more severe than the primary carnitine deficiency caused by defects of the plasma membrane transporter OCTN2 ( SLC22A5) [ 25 , 26 , 27 ]. Recent findings have correlated alterations of CAC expression or regulation with diabetes [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

The Mitochondrial Carnitine Acyl-carnitine Carrier (SLC25A20): Molecular Mechanisms of Transport, Role in Redox Sensing and Interaction with Drugs

et al. 2021

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The SLC25A20 transporter, also known as carnitine acyl-carnitine carrier (CAC), catalyzes the transport of short, medium and long carbon chain acyl-carnitines across the mitochondrial inner membrane in exchange for carnitine. The 30-year story of the protein responsible for this function started with its purification from rat liver mitochondria. Even though its 3D structure is not yet available, CAC is one of the most deeply characterized transport proteins of the inner mitochondrial membrane. Other than functional, kinetic and mechanistic data, post-translational modifications regulating the transport activity of CAC have been revealed. CAC interactions with drugs or xenobiotics relevant to human health and toxicology and the response of the carrier function to dietary compounds have been discovered. Exploiting combined approaches of site-directed mutagenesis with chemical targeting and bioinformatics, a large set of data on structure/function relationships have been obtained, giving novel information on the molecular mechanism of the transport catalyzed by this protein.

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Section: Introductionmentioning

confidence: 99%

The Mitochondrial Carnitine Acyl-carnitine Carrier (SLC25A20): Molecular Mechanisms of Transport, Role in Redox Sensing and Interaction with Drugs

et al. 2021

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“…In this report, they found systemic carnitine deficiency in a child was suffering from hypoketotic hypoglycaemia with seizures that were managed in the early stages of treatment 36 . Previous in vivo study found that hyperinsulinaemia decreased the muscular fatty acyl‐CoA and acyl‐carnitine levels, which are essential factors in biosynthesis of free carnitine 44,45 . The mechanism of hypoglycaemia and/or hyperinsulinaemia‐induced carnitine deficiency is still not fully elucidated.…”

Section: Discussionmentioning

confidence: 93%

Role of carnitine in regulation of blood pressure (MAP/SBP) and gene expression of cardiac hypertrophy markers (α/β‐MHC) during insulin‐induced hypoglycaemia: Role of oxidative stress

Alanazi

Al-Harbi

Imam

et al. 2020

Clin Exp Pharma Physio

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Cardiovascular disease is a leading cause of death in diabetic patients. Hyperglycaemia and iatrogenic hypoglycaemia exacerbate several pathogenic mechanisms underlying hypertension and heart diseases. Carnitine is a potent endogenous antioxidant and cellular fatty acid transporter for antioxidative stress and energy production in the cardiovascular system. The current study aimed to find the role of carnitine in the regulation of hypoglycaemia‐induced hypertension and cardiac hypertrophy. Male rats received insulin glargine (InG) to induce hypoglycaemia followed by D‐carnitine or acetyl‐L‐carnitine for carnitine depletion or carnitine supplementation, respectively. The obtained results showed that carnitine deficiency provoked hypoglycaemia‐induced hypertension. Mean arterial pressure was elevated from 78.16 ± 11.4 to 100 ± 5.11 mm Hg in InG treated group, and from 78.2 ± 8.5 to 123.4 ± 28.2 mm Hg in InG + D‐carnitine treated group. Acetyl‐L‐carnitine resisted the elevation in blood pressure in all hypoglycaemic animals and kept it within the normal values (68.33 ± 6.7 mm Hg). Acetyl‐L‐carnitine increased myocardial carnitine content leading to the attenuation of hypoglycaemia‐induced oxidative stress, which was evaluated through measurement of the oxidative stress biomarkers such as inducible nitric oxide synthase, NAD(P)H quinone dehydrogenase‐1, heme oxygenase‐I, and glutathione S‐transferase. Moreover, acetyl‐L‐carnitine prevented induction of gene expression of cardiac hypertrophy markers during hypoglycaemic conditions, which was assessed via the evaluation of mRNA expression of α‐myosin heavy chain and β‐myosin heavy chain. These findings demonstrate that carnitine might play an essential role in prevention of hypoglycaemia‐induced hypertension and cardiac hypertrophy through providing energy and antioxidants to the cardiovascular system.

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“…SLC16A9 is responsible for carnitine and creatine, which is presumably transported at the basolateral membrane of enterocytes. [ 28 ] SLAC16A9 has also been reported to be associated with some cancer types. Fernandez-Ranvier et al found that SLAC16A9 could be a good diagnostic target for distinguishing benign from malignant adrenocortical tumors.…”

Section: Discussionmentioning

confidence: 99%

Construction of competing endogenous RNA network and identification of novel molecular biomarkers in colon cancer

Liu

et al. 2021

Medicine

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Colon cancer patients suffer from high incidence and mortality rates worldwide. More novel molecular biomarkers should be used for the diagnosis and treatment of colon cancer. Long noncoding RNAs (lncRNAs) are found to be involved in colon cancer tumorigenesis and metastasis. This study aimed to identify novel lncRNAs in colon cancer. Two independent datasets (GSE70880 and GSE110715) were downloaded from the Gene Expression Omnibus database and merged with the sva package. R software was used to distinguish differentially expressed lncRNAs and mRNAs in the merged dataset. The competing endogenous RNA (ceRNA) network was constructed using differentially expressed lncRNAs and mRNAs with Cytoscape. Differentially expressed RNAs in the ceRNA network were further verified using the Cancer Genome Atlas database. Gene oncology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment and survival analysis were also performed to identify hub genes. A total of 99 differentially expressed lncRNAs and 95 differentially expressed mRNAs were identified in the merged database. Ten lncRNAs, 8 miRNAs, and 6 mRNAs were involved in the ceRNA network, in which LINC00114 and UCA1 were highly expressed in colon cancer. They were both associated with early tumor stages and might be used for the early diagnosis of colon cancer. High expression of LINC00114 can lead to poor overall survival of colon cancer patients. Furthermore, new pathways such as LINC00114/miR-107/PCKS5, UCA1/miR-107/PCKS5, and UCA1/miR-129-5p/SEMA6A were identified. Two novel lncRNAs (LINC00114 and UCA1) in colon cancer were identified by bioinformatics analysis. They might contribute to the occurrence and development of colon cancer. In addition, LINC00114 may be involved in the overall survival of colon cancer patients.

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Carnitine Traffic in Cells. Link With Cancer

Cited by 47 publications

References 150 publications

The Mitochondrial Carnitine Acyl-carnitine Carrier (SLC25A20): Molecular Mechanisms of Transport, Role in Redox Sensing and Interaction with Drugs

The Mitochondrial Carnitine Acyl-carnitine Carrier (SLC25A20): Molecular Mechanisms of Transport, Role in Redox Sensing and Interaction with Drugs

Role of carnitine in regulation of blood pressure (MAP/SBP) and gene expression of cardiac hypertrophy markers (α/β‐MHC) during insulin‐induced hypoglycaemia: Role of oxidative stress

Construction of competing endogenous RNA network and identification of novel molecular biomarkers in colon cancer

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