Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion Neurons against Oxidative Insult

Mohammad Sarif Mohiuddin, Tatsuhito Himeno, Rieko Inoue, Emiri Miura-Yura, Yuichiro Yamada, Hiromi Nakai-Shimoda, Saeko Asano, Makoto Kato, Mikio Motegi, Masaki Kondo, Yusuke Seino, Shin Tsunekawa, Yoshiro Kato, Atsushi Suzuki, Keiko Naruse, Koichi Kato, Jiro Nakamura, Hideki Kamiya

研究成果: Article

抄録

Objective. Diabetic polyneuropathy (DPN) is one of the most prevalent diabetic complications. We previously demonstrated that exendin-4 (Ex4), a glucagon-like peptide-1 receptor agonist (GLP-1RA), has beneficial effects in animal models of DPN. We hypothesized that GLP-1 signaling would protect neurons of the peripheral nervous system from oxidative insult in DPN. Here, the therapeutic potential of GLP-1RAs on DPN was investigated in depth using the cellular oxidative insult model applied to the dorsal root ganglion (DRG) neuronal cell line. Research Design and Methods. Immortalized DRG neuronal 50B11 cells were cultured with and without hydrogen peroxide in the presence or absence of Ex4 or GLP-1(7-37). Cytotoxicity and viability were determined using a lactate dehydrogenase assay and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt), respectively. Antioxidant enzyme activity was evaluated using a superoxide dismutase assay. Alteration of neuronal characteristics of 50B11 cells induced by GLP-1RAs was evaluated with immunocytochemistry utilizing antibodies for transient receptor potential vanilloid subfamily member 1, substance P, and calcitonin gene-related peptide. Cell proliferation and apoptosis were also examined by ethynyl deoxyuridine incorporation assay and APOPercentage dye, respectively. The neurite projection ratio induced by treatment with GLP-1RAs was counted. Intracellular activation of adenylate cyclase/cyclic adenosine monophosphate (cAMP) signaling was also quantified after treatment with GLP-1RAs. Results. Neither Ex4 nor GLP-1(7-37) demonstrated cytotoxicity in the cells. An MTS assay revealed that GLP-1RAs amended impaired cell viability induced by oxidative insult in 50B11 cells. GLP-1RAs activated superoxide dismutase. GLP-1RAs induced no alteration of the distribution pattern in neuronal markers. Ex4 rescued the cells from oxidative insult-induced apoptosis. GLP-1RAs suppressed proliferation and promoted neurite projections. No GLP-1RAs induced an accumulation of cAMP. Conclusions. Our findings indicate that GLP-1RAs have neuroprotective potential which is achieved by their direct actions on DRG neurons. Beneficial effects of GLP-1RAs on DPN could be related to these direct actions on DRG neurons.

元の言語English
記事番号9426014
ジャーナルJournal of Diabetes Research
2019
DOI
出版物ステータスPublished - 01-01-2019

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Diabetic Neuropathies
Spinal Ganglia
Neurons
Neurites
Cyclic AMP
Superoxide Dismutase
Tetrazolium Salts
Apoptosis
TRPV Cation Channels
Deoxyuridine
Glucagon-Like Peptide 1
Calcitonin Gene-Related Peptide
Peripheral Nervous System
Diabetes Complications
Substance P
L-Lactate Dehydrogenase
Adenylyl Cyclases
Hydrogen Peroxide
Cultured Cells
Cell Survival

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

これを引用

Mohiuddin, M. S., Himeno, T., Inoue, R., Miura-Yura, E., Yamada, Y., Nakai-Shimoda, H., ... Kamiya, H. (2019). Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion Neurons against Oxidative Insult. Journal of Diabetes Research, 2019, [9426014]. https://doi.org/10.1155/2019/9426014
Mohiuddin, Mohammad Sarif ; Himeno, Tatsuhito ; Inoue, Rieko ; Miura-Yura, Emiri ; Yamada, Yuichiro ; Nakai-Shimoda, Hiromi ; Asano, Saeko ; Kato, Makoto ; Motegi, Mikio ; Kondo, Masaki ; Seino, Yusuke ; Tsunekawa, Shin ; Kato, Yoshiro ; Suzuki, Atsushi ; Naruse, Keiko ; Kato, Koichi ; Nakamura, Jiro ; Kamiya, Hideki. / Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion Neurons against Oxidative Insult. :: Journal of Diabetes Research. 2019 ; 巻 2019.
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title = "Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion Neurons against Oxidative Insult",
abstract = "Objective. Diabetic polyneuropathy (DPN) is one of the most prevalent diabetic complications. We previously demonstrated that exendin-4 (Ex4), a glucagon-like peptide-1 receptor agonist (GLP-1RA), has beneficial effects in animal models of DPN. We hypothesized that GLP-1 signaling would protect neurons of the peripheral nervous system from oxidative insult in DPN. Here, the therapeutic potential of GLP-1RAs on DPN was investigated in depth using the cellular oxidative insult model applied to the dorsal root ganglion (DRG) neuronal cell line. Research Design and Methods. Immortalized DRG neuronal 50B11 cells were cultured with and without hydrogen peroxide in the presence or absence of Ex4 or GLP-1(7-37). Cytotoxicity and viability were determined using a lactate dehydrogenase assay and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt), respectively. Antioxidant enzyme activity was evaluated using a superoxide dismutase assay. Alteration of neuronal characteristics of 50B11 cells induced by GLP-1RAs was evaluated with immunocytochemistry utilizing antibodies for transient receptor potential vanilloid subfamily member 1, substance P, and calcitonin gene-related peptide. Cell proliferation and apoptosis were also examined by ethynyl deoxyuridine incorporation assay and APOPercentage dye, respectively. The neurite projection ratio induced by treatment with GLP-1RAs was counted. Intracellular activation of adenylate cyclase/cyclic adenosine monophosphate (cAMP) signaling was also quantified after treatment with GLP-1RAs. Results. Neither Ex4 nor GLP-1(7-37) demonstrated cytotoxicity in the cells. An MTS assay revealed that GLP-1RAs amended impaired cell viability induced by oxidative insult in 50B11 cells. GLP-1RAs activated superoxide dismutase. GLP-1RAs induced no alteration of the distribution pattern in neuronal markers. Ex4 rescued the cells from oxidative insult-induced apoptosis. GLP-1RAs suppressed proliferation and promoted neurite projections. No GLP-1RAs induced an accumulation of cAMP. Conclusions. Our findings indicate that GLP-1RAs have neuroprotective potential which is achieved by their direct actions on DRG neurons. Beneficial effects of GLP-1RAs on DPN could be related to these direct actions on DRG neurons.",
author = "Mohiuddin, {Mohammad Sarif} and Tatsuhito Himeno and Rieko Inoue and Emiri Miura-Yura and Yuichiro Yamada and Hiromi Nakai-Shimoda and Saeko Asano and Makoto Kato and Mikio Motegi and Masaki Kondo and Yusuke Seino and Shin Tsunekawa and Yoshiro Kato and Atsushi Suzuki and Keiko Naruse and Koichi Kato and Jiro Nakamura and Hideki Kamiya",
year = "2019",
month = "1",
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doi = "10.1155/2019/9426014",
language = "English",
volume = "2019",
journal = "Journal of Diabetes Research",
issn = "2314-6745",
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Mohiuddin, MS, Himeno, T, Inoue, R, Miura-Yura, E, Yamada, Y, Nakai-Shimoda, H, Asano, S, Kato, M, Motegi, M, Kondo, M, Seino, Y, Tsunekawa, S, Kato, Y, Suzuki, A, Naruse, K, Kato, K, Nakamura, J & Kamiya, H 2019, 'Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion Neurons against Oxidative Insult', Journal of Diabetes Research, 巻. 2019, 9426014. https://doi.org/10.1155/2019/9426014

Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion Neurons against Oxidative Insult. / Mohiuddin, Mohammad Sarif; Himeno, Tatsuhito; Inoue, Rieko; Miura-Yura, Emiri; Yamada, Yuichiro; Nakai-Shimoda, Hiromi; Asano, Saeko; Kato, Makoto; Motegi, Mikio; Kondo, Masaki; Seino, Yusuke; Tsunekawa, Shin; Kato, Yoshiro; Suzuki, Atsushi; Naruse, Keiko; Kato, Koichi; Nakamura, Jiro; Kamiya, Hideki.

:: Journal of Diabetes Research, 巻 2019, 9426014, 01.01.2019.

研究成果: Article

TY - JOUR

T1 - Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion Neurons against Oxidative Insult

AU - Mohiuddin, Mohammad Sarif

AU - Himeno, Tatsuhito

AU - Inoue, Rieko

AU - Miura-Yura, Emiri

AU - Yamada, Yuichiro

AU - Nakai-Shimoda, Hiromi

AU - Asano, Saeko

AU - Kato, Makoto

AU - Motegi, Mikio

AU - Kondo, Masaki

AU - Seino, Yusuke

AU - Tsunekawa, Shin

AU - Kato, Yoshiro

AU - Suzuki, Atsushi

AU - Naruse, Keiko

AU - Kato, Koichi

AU - Nakamura, Jiro

AU - Kamiya, Hideki

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective. Diabetic polyneuropathy (DPN) is one of the most prevalent diabetic complications. We previously demonstrated that exendin-4 (Ex4), a glucagon-like peptide-1 receptor agonist (GLP-1RA), has beneficial effects in animal models of DPN. We hypothesized that GLP-1 signaling would protect neurons of the peripheral nervous system from oxidative insult in DPN. Here, the therapeutic potential of GLP-1RAs on DPN was investigated in depth using the cellular oxidative insult model applied to the dorsal root ganglion (DRG) neuronal cell line. Research Design and Methods. Immortalized DRG neuronal 50B11 cells were cultured with and without hydrogen peroxide in the presence or absence of Ex4 or GLP-1(7-37). Cytotoxicity and viability were determined using a lactate dehydrogenase assay and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt), respectively. Antioxidant enzyme activity was evaluated using a superoxide dismutase assay. Alteration of neuronal characteristics of 50B11 cells induced by GLP-1RAs was evaluated with immunocytochemistry utilizing antibodies for transient receptor potential vanilloid subfamily member 1, substance P, and calcitonin gene-related peptide. Cell proliferation and apoptosis were also examined by ethynyl deoxyuridine incorporation assay and APOPercentage dye, respectively. The neurite projection ratio induced by treatment with GLP-1RAs was counted. Intracellular activation of adenylate cyclase/cyclic adenosine monophosphate (cAMP) signaling was also quantified after treatment with GLP-1RAs. Results. Neither Ex4 nor GLP-1(7-37) demonstrated cytotoxicity in the cells. An MTS assay revealed that GLP-1RAs amended impaired cell viability induced by oxidative insult in 50B11 cells. GLP-1RAs activated superoxide dismutase. GLP-1RAs induced no alteration of the distribution pattern in neuronal markers. Ex4 rescued the cells from oxidative insult-induced apoptosis. GLP-1RAs suppressed proliferation and promoted neurite projections. No GLP-1RAs induced an accumulation of cAMP. Conclusions. Our findings indicate that GLP-1RAs have neuroprotective potential which is achieved by their direct actions on DRG neurons. Beneficial effects of GLP-1RAs on DPN could be related to these direct actions on DRG neurons.

AB - Objective. Diabetic polyneuropathy (DPN) is one of the most prevalent diabetic complications. We previously demonstrated that exendin-4 (Ex4), a glucagon-like peptide-1 receptor agonist (GLP-1RA), has beneficial effects in animal models of DPN. We hypothesized that GLP-1 signaling would protect neurons of the peripheral nervous system from oxidative insult in DPN. Here, the therapeutic potential of GLP-1RAs on DPN was investigated in depth using the cellular oxidative insult model applied to the dorsal root ganglion (DRG) neuronal cell line. Research Design and Methods. Immortalized DRG neuronal 50B11 cells were cultured with and without hydrogen peroxide in the presence or absence of Ex4 or GLP-1(7-37). Cytotoxicity and viability were determined using a lactate dehydrogenase assay and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt), respectively. Antioxidant enzyme activity was evaluated using a superoxide dismutase assay. Alteration of neuronal characteristics of 50B11 cells induced by GLP-1RAs was evaluated with immunocytochemistry utilizing antibodies for transient receptor potential vanilloid subfamily member 1, substance P, and calcitonin gene-related peptide. Cell proliferation and apoptosis were also examined by ethynyl deoxyuridine incorporation assay and APOPercentage dye, respectively. The neurite projection ratio induced by treatment with GLP-1RAs was counted. Intracellular activation of adenylate cyclase/cyclic adenosine monophosphate (cAMP) signaling was also quantified after treatment with GLP-1RAs. Results. Neither Ex4 nor GLP-1(7-37) demonstrated cytotoxicity in the cells. An MTS assay revealed that GLP-1RAs amended impaired cell viability induced by oxidative insult in 50B11 cells. GLP-1RAs activated superoxide dismutase. GLP-1RAs induced no alteration of the distribution pattern in neuronal markers. Ex4 rescued the cells from oxidative insult-induced apoptosis. GLP-1RAs suppressed proliferation and promoted neurite projections. No GLP-1RAs induced an accumulation of cAMP. Conclusions. Our findings indicate that GLP-1RAs have neuroprotective potential which is achieved by their direct actions on DRG neurons. Beneficial effects of GLP-1RAs on DPN could be related to these direct actions on DRG neurons.

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DO - 10.1155/2019/9426014

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Mohiuddin MS, Himeno T, Inoue R, Miura-Yura E, Yamada Y, Nakai-Shimoda H その他. Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion Neurons against Oxidative Insult. Journal of Diabetes Research. 2019 1 1;2019. 9426014. https://doi.org/10.1155/2019/9426014