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Updated: Jul 19, 2026

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
Published on: February 24, 2018
NADPH oxidase-derived ROS: key modulators of heme-induced mitochondrial stability in human neutrophils
Maria Augusta Arruda1, Pedro Barcellos-de-Souza, André Luiz Franco Sampaio
1Departamento de Farmacologia, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro 87-Vila Izabel, Rio de Janeiro, RJ, 20551-030 Brazil.
Abstract:
Heme is a proinflammatory molecule able to cause a profound delay of constitutive apoptosis of human neutrophils, an effect that likely contributes to chronic inflammation associated with hemolytic diseases. Herein we show that heme-induced delay of neutrophil apoptosis correlates with the prevention of mitochondrial potential (Deltapsi(m)) dissipation by a mechanism dependent on NADPH oxidase (NADPHox)-generated reactive oxygen species (ROS) and NF-kappaB. Deltapsi(m) maintenance is accompanied by inhibition of Bax insertion into mitochondria and by a decrease in the Bad/Bcl-X(L) ratio. Heme induces Bad degradation in a completely ROS-dependent manner, as well as Bcl-X(L) synthesis, a phenomenon that also requires NF-kappaB activation. These data indicate that heme-induced preservation of mitochondrial integrity is a critical checkpoint controlled by NADPH oxidase generated-ROS and redox-sensitive NF-kappaB activation.
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