High Affinity Carnitine Transporters from OCTN Family in Neural Cells

Januszewicz, Elżbieta; Bekisz, Marek; Mozrzymas, Jerzy W.; Nałęcz, Katarzyna A.

doi:10.1007/s11064-010-0131-5

Cited by 27 publications

(17 citation statements)

References 34 publications

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“…In contrast to pyruvate, lactate, and ketones, ALCAR is transported into cells by members of the organic cation transporter novel family (OCTN2 and 3). These transporters are abundant in astrocytes but are also present in neurons in vivo [40]; however, little is known regarding the regulation of their expression in cultured neurons. The fact that fasting increases the expression of these transporters suggests that their expression could be suppressed by the high glucose and very low fatty acid and ketone body concentrations present in culture media [41].…”

Section: Discussionmentioning

confidence: 99%

Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels

Laird

Clerc

Polster

et al. 2013

Transl. Stroke Res.

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Mitochondrial respiratory capacity is critical for responding to changes in neuronal energy demand. One approach toward neuroprotection is administration of alternative energy substrates (“biofuels”) to overcome brain injury-induced inhibition of glucose-based aerobic energy metabolism. This study tested the hypothesis that exogenous pyruvate, lactate, β-hydroxybutyrate, and acetyl-L-carnitine each increase neuronal respiratory capacity in vitro either in the absence of, or following transient excitotoxic glutamate receptor stimulation. Compared to the presence of 5 mM glucose alone, the addition of pyruvate, lactate, or β-hydroxybutyrate (1.0 – 10.0 mM) to either day in vitro (DIV) 14 or 7 rat cortical neurons resulted in significant, dose-dependent stimulation of respiratory capacity, measured by cell respirometry as the maximal O2 consumption rate in the presence of the respiratory uncoupler FCCP. A thirty minute exposure to 100 μM glutamate impaired respiratory capacity for DIV 14 but not DIV 7 neurons. Glutamate reduced the respiratory capacity for DIV 14 neurons with glucose alone by 25% and also reduced respiratory capacity with glucose plus pyruvate, lactate or β-hydroxybutyrate. However, respiratory capacity in glutamate-exposed neurons following pyruvate or β-hydroxybutyrate addition was still at least as high as that obtained with glucose alone in the absence of glutamate exposure. These results support the interpretation that previously observed neuroprotection by exogenous pyruvate, lactate, or β-hydroxybutyrate is at least partially mediated by their preservation of neuronal respiratory capacity.

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Section: Discussionmentioning

confidence: 99%

Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels

Laird

Clerc

Polster

et al. 2013

Transl. Stroke Res.

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show abstract

“…The level of OCTN2 RNA expression was proved to increase during development in various brain regions [36]. It ought to be added that SLC22A5/OCTN2 was also detected in the brain at the protein level; it is located in the capillary endothelial cells forming the blood-brain barrier ( Figure 2) [29], in astrocytes [12] and in neurons [24].…”

Section: Of 23mentioning

confidence: 98%

“…In accordance with the current classification of solute carriers (SLCs), the carnitine transporters belong to three different families: SLC22, SLC25 and SLC6 (Table 1). [12,19,[22][23][24] * mouse protein; # measurements after reconstitution in liposomes; E-exchange, U-uniport; F-facilitated transport.…”

Section: Carnitine Transportersmentioning

confidence: 99%

SLC22A5 (OCTN2) Carnitine Transporter—Indispensable for Cell Metabolism, a Jekyll and Hyde of Human Cancer

Juraszek

Nałęcz

2019

Molecules

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Oxidation of fatty acids uses l-carnitine to transport acyl moieties to mitochondria in a so-called carnitine shuttle. The process of β-oxidation also takes place in cancer cells. The majority of carnitine comes from the diet and is transported to the cell by ubiquitously expressed organic cation transporter novel family member 2 (OCTN2)/solute carrier family 22 member 5 (SLC22A5). The expression of SLC22A5 is regulated by transcription factors peroxisome proliferator-activated receptors (PPARs) and estrogen receptor. Transporter delivery to the cell surface, as well as transport activity are controlled by OCTN2 interaction with other proteins, such as PDZ-domain containing proteins, protein phosphatase PP2A, caveolin-1, protein kinase C. SLC22A5 expression is altered in many types of cancer, giving an advantage to some of them by supplying carnitine for β-oxidation, thus providing an alternative to glucose source of energy for growth and proliferation. On the other hand, SLC22A5 can also transport several chemotherapeutics used in clinics, leading to cancer cell death.

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“…Immunohistochemical studies show that labeling for OCTN 1, 2 and 3 is distributed in many regions of mouse brain and spinal cord in a pattern consistent with possible roles in modulating bioenergetics and cholinergic neurotransmission [51]. OCTN2 and OCTN3 mRNA and proteins are found in neurons obtained from adult and suckling rat brain [52]…”

Section: L-carnitine Uptake and Metabolic Role In Tissuesmentioning

confidence: 99%

l-Carnitine and Acetyl-l-carnitine Roles and Neuroprotection in Developing Brain

2017

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L-Carnitine functions to transport long chain fatty acyl CoAs into the mitochondria for degradation by β-oxidation. Treatment with L-carnitine can ameliorate metabolic imbalance in many inborn errors of metabolism. In recent years there has been considerable interest in the therapeutic potential of L-carnitine and its acetylated derivative acetyl-L-carnitine (ALCAR) for neuroprotection in a number of disorders including hypoxia-ischemia, traumatic brain injury, Alzheimer’s disease and in conditions leading to central or peripheral nervous system injury. There is compelling evidence from preclinical studies that L-carnitine and ALCAR can improve energy status, decrease oxidative stress and prevent subsequent cell death in models of adult, neonatal and pediatric brain injury. ALCAR can provide an acetyl moiety that can be oxidized for energy, used as a precursor for acetylcholine, or incorporated into glutamate, glutamine and GABA, or into lipids for myelination and cell growth. Administration of ALCAR after brain injury in rat pups improved long-term functional outcomes, including memory. Additional studies are needed to better explore the potential of L-carnitine and ALCAR for protection of developing brain as there is an urgent need for therapies that can improve outcome after neonatal and pediatric brain injury.

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High Affinity Carnitine Transporters from OCTN Family in Neural Cells

Cited by 27 publications

References 34 publications

Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels

Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels

SLC22A5 (OCTN2) Carnitine Transporter—Indispensable for Cell Metabolism, a Jekyll and Hyde of Human Cancer

l-Carnitine and Acetyl-l-carnitine Roles and Neuroprotection in Developing Brain

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