RGD Reference Report - High-intensity training induces EIB in rats through neuron transdifferentiation of adrenal medulla chromaffin cells. - Rat Genome Database

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High-intensity training induces EIB in rats through neuron transdifferentiation of adrenal medulla chromaffin cells.

Authors: He, R  Feng, J  Xun, Q  Qin, Q  Hu, C 
Citation: He R, etal., Am J Physiol Lung Cell Mol Physiol. 2013 May 1;304(9):L602-12. doi: 10.1152/ajplung.00406.2012. Epub 2013 Feb 15.
RGD ID: 9587822
Pubmed: PMID:23418092   (View Abstract at PubMed)
DOI: DOI:10.1152/ajplung.00406.2012   (Journal Full-text)

A high prevalence of exercise-induced bronchoconstriction (EIB) can be found in elite athletes, but the underlying mechanisms remain elusive. Airway responsiveness, NGF and epinephrine (EPI) levels, and chromaffin cell structure in high- (HiTr) and moderate-intensity training (MoTr) rats with or without ovalbumin (OVA) sensitization were measured in a total of 120 male Sprague-Dawley rats. The expression of NGF-associated genes in rat adrenal medulla was tested. Both HiTr and OVA intervention significantly increased airway resistance to aerosolized methacholine measured by whole body plethysmography. HiTr significantly increased inflammatory reaction in the lung with a major increase in peribronchial lymphocyte infiltration, whereas OVA significantly increased the infiltration of various inflammatory cells with an over 10-fold increase in eosinophil level in bronchoalveolar lavage. Both HiTr and OVA intervention upregulated circulating NGF level and peripherin level in adrenal medulla, but downregulated phenylethanolamine N-methyl transferase level in adrenal medulla and circulating EPI level. HiTr + OVA and HiTr + ExhEx (exhaustive exercise) interventions significantly enhanced most of the HiTr effects. The elevated NGF level was significantly associated with neuronal conversion of adrenal medulla chromaffin cells (AMCC). The levels of p-Erk1/2, JMJD3, and Mash1 were significantly increased, but the levels of p-p38 and p-JNK were significantly decreased in adrenal medulla in HiTr and OVA rats. Injection of NGF antiserum and moderate-intensity training reversed these changes observed in HiTr and/or OVA rats. Our study suggests that NGF may play a vital role in the pathogenesis of EIB by inducing neuron transdifferentiation of AMCC via MAPK pathways and subsequently decreasing circulating EPI.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
inflammatory response to antigenic stimulus  IEP 9587822ovalbuminRGD 
response to activity  IEP 9587822 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdm6b  (lysine demethylase 6B)


Additional Information