Suppression of nNOS expression in rat enteric neurones by the receptor for advanced glycation end-products

K. Korenaga, Maria Micci, Giulio Taglialatela, P. J. Pasricha

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Diabetes mellitus results in a loss of neuronal nitric oxide synthase (nNOS) expression in the myenteric plexus but the underlying mechanisms remain unknown. We hypothesized that this may be mediated by advanced glycation end-products (AGEs), a class of modified protein adducts formed by non-enzymatic glycation that interact with the receptor for AGE (RAGE) and which are important in the pathogenesis of other diabetic complications. Whole mount preparations of longitudinal muscles with adherent myenteric plexus (LM-MPs) from the duodenum of adult male rats were exposed to glycated bovines serum albumin (AGE-BSA) or BSA for 24 h. Western blotting, immunohistochemistry and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for mRNA showed a significant reduction in nNOS expression in LM-MPs after exposure to AGE-BSA. NO release, as measured by the Griess reaction, was also significantly reduced by AGE-BSA. A neutralizing antibody against RAGE attenuated the reduction of nNOS protein caused by AGE-BSA. Immunohistochemistry revealed co-localization of RAGE expression with Hu, a marker for neuronal cells but not for S-100, a glial marker. Advanced glycation end-products reduce nNOS expression in the rat myenteric neurones acting via the receptor RAGE. Our results suggest novel pathways for disruption of the nitrergic phenotype in diabetes.

Original languageEnglish (US)
Pages (from-to)392-400
Number of pages9
JournalNeurogastroenterology and Motility
Volume18
Issue number5
DOIs
StatePublished - May 2006

Fingerprint

Nitric Oxide Synthase Type I
Advanced Glycosylation End Products
Myenteric Plexus
Neurons
Immunohistochemistry
Muscles
Diabetes Complications
Neutralizing Antibodies
Reverse Transcriptase Polymerase Chain Reaction
Duodenum
Neuroglia
Real-Time Polymerase Chain Reaction
Diabetes Mellitus
Proteins
Western Blotting
Advanced Glycosylation End Product-Specific Receptor
Phenotype
Messenger RNA

Keywords

  • Advanced glycation end-products
  • Diabetic complications
  • Enteric nervous system
  • Neuronal nitric oxide synthase
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology
  • Neuroscience(all)

Cite this

Suppression of nNOS expression in rat enteric neurones by the receptor for advanced glycation end-products. / Korenaga, K.; Micci, Maria; Taglialatela, Giulio; Pasricha, P. J.

In: Neurogastroenterology and Motility, Vol. 18, No. 5, 05.2006, p. 392-400.

Research output: Contribution to journalArticle

@article{5deb57cdae3a48f5a451d8123a4671ed,
title = "Suppression of nNOS expression in rat enteric neurones by the receptor for advanced glycation end-products",
abstract = "Diabetes mellitus results in a loss of neuronal nitric oxide synthase (nNOS) expression in the myenteric plexus but the underlying mechanisms remain unknown. We hypothesized that this may be mediated by advanced glycation end-products (AGEs), a class of modified protein adducts formed by non-enzymatic glycation that interact with the receptor for AGE (RAGE) and which are important in the pathogenesis of other diabetic complications. Whole mount preparations of longitudinal muscles with adherent myenteric plexus (LM-MPs) from the duodenum of adult male rats were exposed to glycated bovines serum albumin (AGE-BSA) or BSA for 24 h. Western blotting, immunohistochemistry and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for mRNA showed a significant reduction in nNOS expression in LM-MPs after exposure to AGE-BSA. NO release, as measured by the Griess reaction, was also significantly reduced by AGE-BSA. A neutralizing antibody against RAGE attenuated the reduction of nNOS protein caused by AGE-BSA. Immunohistochemistry revealed co-localization of RAGE expression with Hu, a marker for neuronal cells but not for S-100, a glial marker. Advanced glycation end-products reduce nNOS expression in the rat myenteric neurones acting via the receptor RAGE. Our results suggest novel pathways for disruption of the nitrergic phenotype in diabetes.",
keywords = "Advanced glycation end-products, Diabetic complications, Enteric nervous system, Neuronal nitric oxide synthase, Nitric oxide",
author = "K. Korenaga and Maria Micci and Giulio Taglialatela and Pasricha, {P. J.}",
year = "2006",
month = "5",
doi = "10.1111/j.1365-2982.2006.00774.x",
language = "English (US)",
volume = "18",
pages = "392--400",
journal = "Neurogastroenterology and Motility",
issn = "1350-1925",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Suppression of nNOS expression in rat enteric neurones by the receptor for advanced glycation end-products

AU - Korenaga, K.

AU - Micci, Maria

AU - Taglialatela, Giulio

AU - Pasricha, P. J.

PY - 2006/5

Y1 - 2006/5

N2 - Diabetes mellitus results in a loss of neuronal nitric oxide synthase (nNOS) expression in the myenteric plexus but the underlying mechanisms remain unknown. We hypothesized that this may be mediated by advanced glycation end-products (AGEs), a class of modified protein adducts formed by non-enzymatic glycation that interact with the receptor for AGE (RAGE) and which are important in the pathogenesis of other diabetic complications. Whole mount preparations of longitudinal muscles with adherent myenteric plexus (LM-MPs) from the duodenum of adult male rats were exposed to glycated bovines serum albumin (AGE-BSA) or BSA for 24 h. Western blotting, immunohistochemistry and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for mRNA showed a significant reduction in nNOS expression in LM-MPs after exposure to AGE-BSA. NO release, as measured by the Griess reaction, was also significantly reduced by AGE-BSA. A neutralizing antibody against RAGE attenuated the reduction of nNOS protein caused by AGE-BSA. Immunohistochemistry revealed co-localization of RAGE expression with Hu, a marker for neuronal cells but not for S-100, a glial marker. Advanced glycation end-products reduce nNOS expression in the rat myenteric neurones acting via the receptor RAGE. Our results suggest novel pathways for disruption of the nitrergic phenotype in diabetes.

AB - Diabetes mellitus results in a loss of neuronal nitric oxide synthase (nNOS) expression in the myenteric plexus but the underlying mechanisms remain unknown. We hypothesized that this may be mediated by advanced glycation end-products (AGEs), a class of modified protein adducts formed by non-enzymatic glycation that interact with the receptor for AGE (RAGE) and which are important in the pathogenesis of other diabetic complications. Whole mount preparations of longitudinal muscles with adherent myenteric plexus (LM-MPs) from the duodenum of adult male rats were exposed to glycated bovines serum albumin (AGE-BSA) or BSA for 24 h. Western blotting, immunohistochemistry and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for mRNA showed a significant reduction in nNOS expression in LM-MPs after exposure to AGE-BSA. NO release, as measured by the Griess reaction, was also significantly reduced by AGE-BSA. A neutralizing antibody against RAGE attenuated the reduction of nNOS protein caused by AGE-BSA. Immunohistochemistry revealed co-localization of RAGE expression with Hu, a marker for neuronal cells but not for S-100, a glial marker. Advanced glycation end-products reduce nNOS expression in the rat myenteric neurones acting via the receptor RAGE. Our results suggest novel pathways for disruption of the nitrergic phenotype in diabetes.

KW - Advanced glycation end-products

KW - Diabetic complications

KW - Enteric nervous system

KW - Neuronal nitric oxide synthase

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=33645812741&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645812741&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2982.2006.00774.x

DO - 10.1111/j.1365-2982.2006.00774.x

M3 - Article

VL - 18

SP - 392

EP - 400

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

SN - 1350-1925

IS - 5

ER -