Dataset Information

Molecular cloning, tissue distribution and the expression of cystine/glutamate exchanger (xCT, SLC7A11) in different tissues during development in broiler chickens.

ABSTRACT: The cystine/glutamate exchanger (xCT, SLC7A11) is a component of the system Xc amino-acid antiporter that is able to export glutamate and import cysteine into cells. The xCT amino acid exchanger has received a lot of attention, due to the fact that cysteine is an essential substrate for the synthesis of glutathione (GSH), an endogenous antioxidant in cells. The objective of this research was to clone the full-length cDNA of chicken xCT, and to investigate the gene expression of xCT in different tissues, including intestinal segments of broiler chickens during development. The full-length cDNA of chicken xCT (2,703 bp) was obtained from the jejunum by reverse transcription-PCR and sequenced. Homology tests showed that chicken xCT had 80.4%, 80.2%, and 71.2% homology at the nucleotide level with humans, cattle, and rats, respectively. Likewise, amino acid sequence analysis showed that chicken xCT protein is 86.4%, 79.3%, and 75.6% homologous with humans, cattle, and rats, respectively. Additionally, phylogenetic analysis indicated that chicken xCT genes share a closer genetic relationship with humans and cattle, than with rats. The chicken xCT protein has 12 transmembrane helixes, 6 extracellular loops, and 5 intracellular loops. The mRNA of xCT was detected in all tissues, including intestinal segments, in which the mRNA expression of xCT was significantly higher (P < 0.05) within the colon, compared to the jejunum and ileum. During development, a linear pattern of changes regarding the levels of the xCT mRNA was found, indicating that there was an abundance of xCT within the duodenum (P < 0.05). Furthermore, there were changes of the xCT mRNA abundance in the colon during development, which displayed linear and cubic patterns (P < 0.05). These results indicated that xCT is widely expressed both in intestinal segments, as well as other organs that are not associated with nutrient absorption. Further investigation is needed to characterize the functional relevance of xCT activity in oxidative stress and inflammation in the small intestine of broiler chickens.

SUBMITTER: Choi J

PROVIDER: S-EPMC7082690 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Molecular cloning, tissue distribution and the expression of cystine/glutamate exchanger (xCT, SLC7A11) in different tissues during development in broiler chickens.

Choi Janghan J Li Weiqi W Schindell Brayden B Ni Liju L Liu Shangxi S Zhao Xiaoya X Gong Joshua J Nyachoti Martin M Yang Chengbo C

Animal nutrition (Zhongguo xu mu shou yi xue hui) 20191031 1

The cystine/glutamate exchanger (xCT, SLC7A11) is a component of the system X<sub>c</sub> amino-acid antiporter that is able to export glutamate and import cysteine into cells. The xCT amino acid exchanger has received a lot of attention, due to the fact that cysteine is an essential substrate for the synthesis of glutathione (GSH), an endogenous antioxidant in cells. The objective of this research was to clone the full-length cDNA of chicken xCT, and to investigate the gene expression of xCT in ...[more]

PMID: 32211536

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Project description:xCT is the specific chain of the cystine/glutamate antiporter, which is widely reported to support anti-oxidant defenses in vivo. xCT is therefore at the crossroads between two processes that are involved in schizophrenia: oxidative stress and glutamatergic neurotransmission. But data from human studies implicating xCT in the illness and clarifying the upstream mechanisms of xCT imbalance are still scarce. Low glutathione (GSH) levels and genetic risk in GCLC (Glutamate-Cysteine Ligase Catalytic subunit), the gene of limiting synthesizing enzyme for GSH, are both associated with schizophrenia. In the present study, we aimed at determining if xCT regulation by the redox system is involved in schizophrenia pathophysiology. We assessed whether modulating GCLC expression impact on xCT expression and activity (i) in fibroblasts from patients and controls with different GCLC genotypes which are known to affect GCLC regulation and GSH levels; (ii) in rat brain glial cells, i.e., astrocytes and oligodendrocytes, with a knock-down of GCLC. Our results highlight that decreased GCLC expression leads to an upregulation of xCT levels in patients' fibroblasts as well as in astrocytes. These results support the implication of xCT dysregulation in illness pathophysiology and further indicate that it can result from redox changes. Additionally, we showed that these anomalies may already take place at early stages of psychosis and be more prominent in a subgroup of patients with GCLC high-risk genotypes. These data add to the existing evidence identifying the inflammatory/redox systems as important targets to treat schizophrenia already at early stages.SchizophreniaANTIOXIDANT DEFICIT INCREASES A KEY NEUROTRANSMITTER TRANSPORTER: Deficit of antioxidant synthesis in schizophrenia leads to oxidative stress and changes in neurotransmitter transporter. Led by Kim Do, a team of researchers from Lausanne University in Switzerland investigated the role of the cell-surface transport protein xCT in schizophrenia. They found that an enzyme responsible for antioxidant production is disturbed in patients. This leads to decreased antioxidant levels and consequently to oxidative stress-i.e. the accumulation of reactive oxygen molecules, damaging the cells component and impairing cell functioning-which in turn affects the functioning of the antioxidant pathway, including xCT. xCT, which exports the neurotransmitter glutamate, is thus overproduced in schizophrenia. The resulting increase of neurotransmitter activity, alongside the increase in oxidative stress, is thought to play a major role in the pathophysiology of schizophrenia, including at early stages of the disease.

Dataset Information

Molecular cloning, tissue distribution and the expression of cystine/glutamate exchanger (xCT, SLC7A11) in different tissues during development in broiler chickens.

Publications

Molecular cloning, tissue distribution and the expression of cystine/glutamate exchanger (xCT, SLC7A11) in different tissues during development in broiler chickens.

Similar Datasets

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