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Vascular targets of redox signalling in diabetes mellitus
1Department of Medical Biochemistry and Medical Molecular Biology, Karl-Franzens University of Graz, Graz, Austria.
Abstract:
There is overwhelming evidence for an involvement of reactive oxygen species (ROS) in the pathogenesis of diabetes-associated vascular complications. However, neither the exact source of the ROS initiating cascades leading to cell dysfunction in diabetes nor their chemical nature is fully understood. Furthermore, despite our knowledge of the crucial role of ROS in diabetes, little is known about the actual targets and the molecular consequences of the interaction of ROS with cellular signalling pathways. Therefore, we aim to provide an overview of ROS (i.e. O2(*-), NO*, ONOO- and H2O2) and their vascular sources in diabetes and to summarise recent knowledge on the mechanisms underlying increased ROS production within the vascular wall. In addition, possible targets of diabetes and ROS within the vasculature are discussed. These include, the effects of ROS on small guanine nucleotide binding proteins, the cytoskeleton, protein kinases (e.g tyrosine kinases), metalloproteinases, ion homeostasis and transcriptional regulation. Such analysis makes it clear that the generation of ROS could affect a large number of various signalling pathways and proteins. Thus, a better knowledge of the functional diversity and pathological consequences of each individual pathway activated by ROS id essential to understand the mechanisms of diabetes-associated vascular complications.
Insights
Reactive oxygen species (ROS) contribute to diabetes complications. This study reviews ROS sources, targets, and molecular effects in blood vessels to clarify their role in disease.
Area of Science:
- Vascular Biology
- Diabetes Pathophysiology
- Oxidative Stress
Background:
- Reactive oxygen species (ROS) are implicated in diabetes-associated vascular complications.
- The precise sources and chemical nature of ROS in diabetes remain unclear.
- Knowledge gaps exist regarding ROS targets and molecular consequences in diabetic vascular signaling.
Purpose of the Study:
- To provide an overview of ROS and their vascular sources in diabetes.
- To summarize mechanisms of increased ROS production in the vascular wall.
- To discuss potential targets of ROS within the diabetic vasculature.
Main Methods:
- Literature review and synthesis of existing research on ROS in diabetes.
- Analysis of ROS types including superoxide radical (O2(*-)), nitric oxide radical (NO*), peroxynitrite (ONOO-), and hydrogen peroxide (H2O2).
- Discussion of molecular targets and signaling pathways affected by ROS.
Main Results:
- ROS production is increased in the diabetic vascular wall through various mechanisms.
- ROS impact multiple cellular targets, including small GTPases, cytoskeleton, protein kinases, metalloproteinases, ion channels, and transcriptional regulators.
- ROS affect numerous signaling pathways and proteins within the vasculature.
Conclusions:
- Understanding the functional diversity and pathological consequences of ROS-activated pathways is crucial.
- Elucidating ROS mechanisms is essential for comprehending diabetes-associated vascular complications.
- Further research is needed to fully understand the complex role of ROS in diabetic vascular disease.