Correlation between NADPH oxidase and protein kinase C in the ROS production by human granulocytes related to age.
BACKGROUND
Aging may be defined as gradual and progressive changes in an organism that increase the probability of death. Accumulating evidence now indicates that the sum of deleterious free radical reactions going on continuously throughout cells and tissues constitutes the aging process or is a major contributor to it.


OBJECTIVE
The aim of this paper was to study the correlation between NADPH oxidase and protein kinase C (PKC) in the reactive oxygen species (ROS) production related to age.


METHODS
The age-induced ROS generation was studied in healthy subjects ranging in age from 20 to 80 years, divided into six age groups: (1) 20-29, (2) 30-39, (3) 40-49, (4) 50-59, (5) 60-69, and (6) 70-80 years. The ROS were quantified using a chemiluminescence assay (luminol dependent) and the results expressed as RLU/s at maximum peak and total chemiluminescence (integral under the curve RLU/s).


RESULTS
Our results demonstrate a significant increase of the ROS production from 40 years of age (age groups 3-6). In the age groups 1 and 2, we did not observe a significant difference (p > 0.05). These data suggest an increase of the ROS production from 40 to 49 years of age which may be induced by the PKC activity. The selective PKC inhibitor (calphostin C) abrogated the stimulatory effect of phorbol-12,13-dibutyrate on the ROS production. However, the NADPH oxidase inhibitor diphenylene iodonium did not inhibit the total ROS production by granulocytes in relation to age.


CONCLUSIONS
These data suggest a correlation between age-related PKC activity, NADPH oxidase phosphorylation, and ROS production. The above correlations between unspecific and inflammatory responses related to age are discussed.
Martins Chaves
Míriam
M
Departamento de Bioquímica e Imunología, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. chavesmm@icb.ufmg.br
Prates Rodrigues
Andreia Laura
AL
Pereira dos Reis
Ataualpa
A
Gerzstein
Nestor Carlos
NC
Nogueira-Machado
José Augusto
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D009861:Onium Compounds; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; D019255:NADPH Oxidases; D011493:Protein Kinase C; C058819:calphostin C