Correlation between NADPH Oxidase and Protein Kinase C in the ROS Production by Human Granulocytes Related to Age

Abstract

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.

Suppression of ROS generation by 4,4'-diaminodiphenylsulfone in non-phagocytic human diploid fibroblasts

“…The increased calcium might activate the calcium-dependent events such as PKC activation, required for NOX activation. The association of paraquat-induced superoxide anion generation with activation of PKC is well established (Martins et al, 2002;Miller et al, 2007). Therefore, it was asked whether DDS could modulate PKC activation.…”

“…PKC is involved in the ligand-initiated assembly of NADPH oxidase (NOX) for the generation of superoxide anions (Martins et al, 2002). Recently, paraquat has been shown to induce ROS through activation of PKC-delta dependent NOX (Miller et al, 2007).…”

Immobilization stress induces cell death through production of reactive oxygen species in the mouse cerebral cortex

“…NADPH oxidase contributes directly to oxidative stress [27] by producing increased levels of ROS [12,13], which have been shown to induce cell death in cultured cerebellar granule neurons [20,28]. It has also been documented that ROS production is detected in increased expression of oxidative stress, and increased ROS production and oxidative stress propagation contribute to chronic intermittent hypoxiamediated cortical neuronal apoptosis [30].…”

Rebamipide affects the efficiency of colchicine for the herpes simplex virus-induced inflammation in a Behcet's disease mouse model

“…Fas system dysregulation leads to uncontrolled lymphoproliferation, indicating that the Fas/FasL system plays a central role in immune reaction control via cell death activation (Chervonsky et al, 1997;Nishimura et al, 1997). NADPH oxidase contributes directly to oxidative stress (Tammariello et al, 2000) by producing increased levels of ROS (Martins Chaves et al, 2002). It has also been documented that ROS production is detected in increased expression of oxidative stress and increased ROS production and oxidative stress propagation contribute to chronic inflammation (Afonso et al, 2007).…”