CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution.

Autor: Wang Q; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. qinchuan.wang@jhmi.edu., Hernández-Ochoa EO; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA., Viswanathan MC; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA., Blum ID; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Do DC; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA., Granger JM; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA., Murphy KR; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA., Wei AC; Department of Electrical Engineering, Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan., Aja S; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Center for Metabolism and Obesity Research, Johns Hopkins School of Medicine, Baltimore, MD, USA., Liu N; Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, MD, USA., Antonescu CM; Johns Hopkins Computational Biology Consulting Core, Baltimore, MD, USA., Florea LD; Johns Hopkins Computational Biology Consulting Core, Baltimore, MD, USA., Talbot CC Jr; Institute for Basic Biomedical Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Mohr D; Johns Hopkins School of Medicine Genetic Resources Core Facility, Baltimore, MD, USA., Wagner KR; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, MD, USA., Regot S; Department of Molecular Biology & Genetics, Johns Hopkins School of Medicine, Baltimore, MD, USA., Lovering RM; Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA., Gao P; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA., Bianchet MA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD, USA., Wu MN; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Cammarato A; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA., Schneider MF; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA., Bever GS; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Center for Functional Anatomy & Evolution, Johns Hopkins School of Medicine, Baltimore, MD, USA., Anderson ME; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. mark.anderson@jhmi.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 May 26; Vol. 12 (1), pp. 3175. Date of Electronic Publication: 2021 May 26.
DOI: 10.1038/s41467-021-23549-3
Abstrakt: Antagonistic pleiotropy is a foundational theory that predicts aging-related diseases are the result of evolved genetic traits conferring advantages early in life. Here we examine CaMKII, a pluripotent signaling molecule that contributes to common aging-related diseases, and find that its activation by reactive oxygen species (ROS) was acquired more than half-a-billion years ago along the vertebrate stem lineage. Functional experiments using genetically engineered mice and flies reveal ancestral vertebrates were poised to benefit from the union of ROS and CaMKII, which conferred physiological advantage by allowing ROS to increase intracellular Ca 2+ and activate transcriptional programs important for exercise and immunity. Enhanced sensitivity to the adverse effects of ROS in diseases and aging is thus a trade-off for positive traits that facilitated the early and continued evolutionary success of vertebrates.
Databáze: MEDLINE