Essential role of complex II of the respiratory chain in hypoxia-induced ROS generation in the pulmonary vasculature

In the pulmonary vasculature, the mechanisms responsible for oxygen sensing and the initiation of hypoxia-induced vasoconstriction and vascular remodeling are still unclear. Nitric oxide (NO) and reactive oxygen species (ROS) are discussed as early mediators of the hypoxic response. Here, we describ...

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Published in:American journal of physiology. Lung cellular and molecular physiology 2003-05, Vol.28 (5), p.L710-L719
Main Authors: PADDENBERG, Renate, ISHAQ, Barat, GOLDENBERG, Anna, FAULHAMMER, Petra, ROSE, Frank, WEISSMANN, Norbert, BRAUN-DULLAEUS, Ruediger C, KUMMER, Wolfgang
Format: Article
Language:English
Subjects:
Biological and medical sciences
Medical sciences
Oxygen
Pneumology
Pulmonary arteries
Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases
Respiratory system
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Summary:In the pulmonary vasculature, the mechanisms responsible for oxygen sensing and the initiation of hypoxia-induced vasoconstriction and vascular remodeling are still unclear. Nitric oxide (NO) and reactive oxygen species (ROS) are discussed as early mediators of the hypoxic response. Here, we describe a quantitative analysis of NO- and ROS-producing cells within the vascular walls of murine lung sections cultured at normoxia or hypoxia. Whereas the number of NO-producing cells was not changed by hypoxia, the number of ROS-generating cells was significantly increased. Addition of specific inhibitors revealed that mitochondria were the source of ROS. The participation of the individual mitochondrial complexes differed in normoxic and hypoxic ROS generation. Whereas normoxic ROS production required complexes I and III, hypoxic ROS generation additionally demanded complex II. Histochemically demonstrable succinate dehydrogenase activity of complex II in the arterial wall decreased during hypoxia. Inhibition of the reversed enzymatic reaction, i.e., fumarate reductase, by application of succinate, specifically abolished hypoxic, but not normoxic, ROS generation. Thus complex II plays an essential role in hypoxic ROS production. Presumably, its catalytic activity switches from succinate dehydrogenase to fumarate reductase at reduced oxygen tension, thereby modulating the directionality of the electron flow. [PUBLICATION ABSTRACT]
ISSN:1040-0605
1522-1504