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Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia

Phosphoinositides (PIs) play important roles in the structure and function of the brain. Associations between PIs and the pathophysiology of schizophrenia have been studied. However, the significance of the PI metabolic pathway in the pathology of schizophrenia is unknown. We examined the expression...

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Autores principales: Kunii, Yasuto, Matsumoto, Junya, Izumi, Ryuta, Nagaoka, Atsuko, Hino, Mizuki, Shishido, Risa, Sainouchi, Makoto, Akatsu, Hiroyasu, Hashizume, Yoshio, Kakita, Akiyoshi, Yabe, Hirooki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348881/
https://www.ncbi.nlm.nih.gov/pubmed/34361045
http://dx.doi.org/10.3390/ijms22158280
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author Kunii, Yasuto
Matsumoto, Junya
Izumi, Ryuta
Nagaoka, Atsuko
Hino, Mizuki
Shishido, Risa
Sainouchi, Makoto
Akatsu, Hiroyasu
Hashizume, Yoshio
Kakita, Akiyoshi
Yabe, Hirooki
author_facet Kunii, Yasuto
Matsumoto, Junya
Izumi, Ryuta
Nagaoka, Atsuko
Hino, Mizuki
Shishido, Risa
Sainouchi, Makoto
Akatsu, Hiroyasu
Hashizume, Yoshio
Kakita, Akiyoshi
Yabe, Hirooki
author_sort Kunii, Yasuto
collection PubMed
description Phosphoinositides (PIs) play important roles in the structure and function of the brain. Associations between PIs and the pathophysiology of schizophrenia have been studied. However, the significance of the PI metabolic pathway in the pathology of schizophrenia is unknown. We examined the expression of PI signaling-associated proteins in the postmortem brain of schizophrenia patients. Protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA, also known as PIK4A), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), protein kinase B (Akt), and glycogen synthase kinase 3β (GSK3β) were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays of the prefrontal cortex (PFC) of postmortem samples from 23 schizophrenia patients and 47 normal controls. We also examined the association between PIK4CA expression and its genetic variants in the same brain samples. PIK4CA expression was lower, whereas Akt expression was higher, in the PFC of schizophrenia patients than in that of controls; PIP5K1C, PTEN, and GSK3β expression was not different. No single-nucleotide polymorphism significantly affected protein expression. We identified molecules involved in the pathology of schizophrenia via this lipid metabolic pathway. These results suggest that PIK4CA is involved in the mechanism underlying the pathogenesis of schizophrenia and is a potential novel therapeutic target.
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spelling pubmed-83488812021-08-08 Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia Kunii, Yasuto Matsumoto, Junya Izumi, Ryuta Nagaoka, Atsuko Hino, Mizuki Shishido, Risa Sainouchi, Makoto Akatsu, Hiroyasu Hashizume, Yoshio Kakita, Akiyoshi Yabe, Hirooki Int J Mol Sci Article Phosphoinositides (PIs) play important roles in the structure and function of the brain. Associations between PIs and the pathophysiology of schizophrenia have been studied. However, the significance of the PI metabolic pathway in the pathology of schizophrenia is unknown. We examined the expression of PI signaling-associated proteins in the postmortem brain of schizophrenia patients. Protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA, also known as PIK4A), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), protein kinase B (Akt), and glycogen synthase kinase 3β (GSK3β) were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays of the prefrontal cortex (PFC) of postmortem samples from 23 schizophrenia patients and 47 normal controls. We also examined the association between PIK4CA expression and its genetic variants in the same brain samples. PIK4CA expression was lower, whereas Akt expression was higher, in the PFC of schizophrenia patients than in that of controls; PIP5K1C, PTEN, and GSK3β expression was not different. No single-nucleotide polymorphism significantly affected protein expression. We identified molecules involved in the pathology of schizophrenia via this lipid metabolic pathway. These results suggest that PIK4CA is involved in the mechanism underlying the pathogenesis of schizophrenia and is a potential novel therapeutic target. MDPI 2021-07-31 /pmc/articles/PMC8348881/ /pubmed/34361045 http://dx.doi.org/10.3390/ijms22158280 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kunii, Yasuto
Matsumoto, Junya
Izumi, Ryuta
Nagaoka, Atsuko
Hino, Mizuki
Shishido, Risa
Sainouchi, Makoto
Akatsu, Hiroyasu
Hashizume, Yoshio
Kakita, Akiyoshi
Yabe, Hirooki
Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia
title Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia
title_full Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia
title_fullStr Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia
title_full_unstemmed Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia
title_short Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia
title_sort evidence for altered phosphoinositide signaling-associated molecules in the postmortem prefrontal cortex of patients with schizophrenia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348881/
https://www.ncbi.nlm.nih.gov/pubmed/34361045
http://dx.doi.org/10.3390/ijms22158280
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