TY - JOUR
T1 - Reactive Oxygen Comes of Age
T2 - Mechanism-Based Therapy of Diabetic End-Organ Damage
AU - Elbatreek, Mahmoud H.
AU - Pachado, Mayra P.
AU - Cuadrado, Antonio
AU - Jandeleit-Dahm, Karin
AU - Schmidt, Harald H. H. W.
N1 - Funding Information:
The authors wish to thank Dr Merlijn J Meens and Dr Hermann Mucke for critically reading the manuscript and/or helpful suggestions. H.H.H.W.S. wishes to gratefully acknowledge funding by an ERC Advanced Investigator Grant (294683 – RadMed), an ERC proof-of-concept grant (139-101052 – SAVEBRAIN), and the EU Horizon 2020 programme, REPO-TRIAL. K.J.D. is supported by a fellowship of the National Health and Medical Research Council. A.C. is the recipient of grant SAF2016-76520-R from the Spanish Ministry of Economy and Competitiveness, P_37_732/2016 REDBRAIN from the European Regional Development Fund, and the Competitiveness Operational Program 2014-2020.
Funding Information:
The authors wish to thank Dr Merlijn J Meens and Dr Hermann Mucke for critically reading the manuscript and/or helpful suggestions. H.H.H.W.S. wishes to gratefully acknowledge funding by an ERC Advanced Investigator Grant (294683 ? RadMed), an ERC proof-of-concept grant (139-101052 ? SAVEBRAIN), and the EU Horizon 2020 programme, REPO-TRIAL. K.J.D. is supported by a fellowship of the National Health and Medical Research Council. A.C. is the recipient of grant SAF2016-76520-R from the Spanish Ministry of Economy and Competitiveness, P_37_732/2016 REDBRAIN from the European Regional Development Fund, and the Competitiveness Operational Program 2014-2020.
Funding Information:
The authors wish to thank Dr Merlijn J Meens and Dr Hermann Mucke for critically reading the manuscript and/or helpful suggestions. H.H.H.W.S. wishes to gratefully acknowledge funding by an ERC Advanced Investigator Grant ( 294683 – RadMed), an ERC proof-of-concept grant ( 139-101052 – SAVEBRAIN), and the EU Horizon 2020 programme, REPO-TRIAL. K.J.D. is supported by a fellowship of the National Health and Medical Research Council . A.C. is the recipient of grant SAF2016-76520-R from the Spanish Ministry of Economy and Competitiveness , P_37_732/2016 REDBRAIN from the European Regional Development Fund , and the Competitiveness Operational Program 2014-2020.
Publisher Copyright:
© 2019 The Authors
PY - 2019/5
Y1 - 2019/5
N2 - Reactive oxygen species (ROS) have been mainly viewed as unwanted by-products of cellular metabolism, oxidative stress, a sign of a cellular redox imbalance, and potential disease mechanisms, such as in diabetes mellitus (DM). Antioxidant therapies, however, have failed to provide clinical benefit. This paradox can be explained by recent discoveries that ROS have mainly essential signaling sources. Disease can occur when ROS accumulate in nonphysiological concentrations, locations, or forms. By focusing on disease-relevant sources and targets of ROS, and leaving ROS physiology intact, precise therapeutic interventions are now possible and are entering clinical trials. Their outcomes are likely to profoundly change our concepts of ROS in DM and in medicine in general.
AB - Reactive oxygen species (ROS) have been mainly viewed as unwanted by-products of cellular metabolism, oxidative stress, a sign of a cellular redox imbalance, and potential disease mechanisms, such as in diabetes mellitus (DM). Antioxidant therapies, however, have failed to provide clinical benefit. This paradox can be explained by recent discoveries that ROS have mainly essential signaling sources. Disease can occur when ROS accumulate in nonphysiological concentrations, locations, or forms. By focusing on disease-relevant sources and targets of ROS, and leaving ROS physiology intact, precise therapeutic interventions are now possible and are entering clinical trials. Their outcomes are likely to profoundly change our concepts of ROS in DM and in medicine in general.
KW - NITRIC-OXIDE SYNTHASE
KW - SOLUBLE GUANYLATE-CYCLASE
KW - NADPH OXIDASE
KW - OXIDATIVE STRESS
KW - BARDOXOLONE METHYL
KW - HYDROGEN-PEROXIDE
KW - ENDOTHELIAL DYSFUNCTION
KW - INSULIN-RESISTANCE
KW - L-ARGININE
KW - NAD(P)H OXIDASE
U2 - 10.1016/j.tem.2019.02.006
DO - 10.1016/j.tem.2019.02.006
M3 - (Systematic) Review article
C2 - 30928357
SN - 1043-2760
VL - 30
SP - 312
EP - 327
JO - Trends in Endocrinology and Metabolism
JF - Trends in Endocrinology and Metabolism
IS - 5
ER -