Experimental Section

Role of Inositol 1,4,5-Triphosphate and p38 Mitogen-Activated Protein Kinase in Reactive Oxygen Species Generation by Granulocytes in a Cyclic AMP-Dependent Manner: An Age-Related Phenomenon
Míriam Martins Chaves^a, Daniela Caldeira Costa^a, Cristina Costa Telhado Pereira^a, Thiago Rabelo Andrade^a, Bernardo Coelho Horta^a, José Augusto Nogueira-Machado<sup>b

a</sup>Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, and
^bSanta Casa Hospital of Belo Horizonte, Belo Horizonte, Brazil

Address of Corresponding Author

Gerontology 2007;53:228-233 (DOI: 10.1159/000100960)

  Key Words

• Age-related signal transduction
• Neutrophils
• Protein kinase A
• p38 Mitogen-activated protein kinase
• Inositol 1,4,5-triphosphate

  Abstract

Background: It is generally agreed that elderly subjects undergo progressive deterioration of their immune responsiveness, which leads to an increased susceptibility to autoimmune processes, neoplasm and inflammation. Thus there is a general consensus that regulation of inflammation results from a balance between pro-inflammatory and anti-inflammatory pathways. Objective: The present study aimed to investigate the possible alterations of cyclic AMP/protein kinase A (cAMP/PKA) and p38 mitogen-activated protein kinase (p38 MAPK) pathway signaling (reactive oxygen species (ROS) generation) and inositol 1,4,5-triphosphate (InsP3) production by neutrophils during the aging process. Methods: Age-induced ROS generation and InsP3 production were studied in healthy subjects ranging in age from 20 to 80 years. The subjects were divided into six age groups: (I) 20-29, (II) 30-39, (III) 40-49, (IV) 50-59, (V) 60-69, and (VI) 70-80 years old. The effect of cAMP, H89 (inhibitor PKA), and PD169316 (inhibitor p38 MAPK) on ROS production was quantified in a luminol-dependent chemiluminescence assay (relative light units/min) and by InsP3 release (cpm). Results: Our results demonstrated a lack of dibutyryl cAMP inhibitory effects on ROS generation and InsP3 production by granulocytes from PKA-dependent 50-year-olds. However, the inhibitory effect of cAMP is restored in neutrophils after the age of 50 years when p38 MAPK signaling is inhibited. Conclusions: The present study may be important towards a better understanding of the high susceptibility to infections and age-related inflammatory and deregulation diseases. The alteration of cAMP/PKA and p38 MAPK signaling pathways enhances the inflammatory process.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Dr. Míriam Martins Chaves
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas
Universidade Federal de Minas Gerais, Caixa Postal 486
30161-970, Belo Horizonte/Minas Gerais (Brazil)
Tel. +55 31 3499 2660, Fax +55 31 3499 2614, E-Mail chavesmm@icb.ufmg.br

  Article Information

Received: October 22, 2006
Accepted: January 17, 2007
Published online: March 20, 2007
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 2, Number of References : 21