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T cell mitochondrial ROS in development of hypertension (693.15)
Author(s) -
Nazarewicz Rafal,
Dikalova Anna,
Bikineyeva Alfiya,
Egnatchik Rob,
Young Jamey,
Harrison David,
Dikalov Sergey
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.693.15
Subject(s) - mitochondrial ros , mitochondrion , reactive oxygen species , anaerobic glycolysis , chemistry , angiotensin ii , superoxide , microbiology and biotechnology , glycolysis , pharmacology , medicine , endocrinology , biology , metabolism , biochemistry , receptor , enzyme
T cell mitochondrial ROS in development of hypertension Rafal R. Nazarewicz *, Anna Dikalova*, Alfiya Bikineyeva*, Rob Egnatchik # , Jamey Young # , David G. Harrison*, Sergey Dikalov* Division of Clinical Pharmacology*, Chemical and Biomolecular Engineering # , Vanderbilt University Medical Center, Nashville, TN Immunity plays a key role in the development of hypertension. Locally acting T cells secret pro‐inflammatory cytokines that have profound damaging effects on end‐organs and facilitate hypertension. Mitochondrial ROS may contribute to regulation of T cells activity and cytokine production by switching from aerobic mitochondria‐base metabolism to anaerobic glycolysis. The objective of this study was to establish the role of T cell mitochondrial ROS in development of hypertension. Increased mitochondrial superoxide and H 2 O 2 in T cells from hypertensive mice was inhibited by overexpression of catalase in mitochondria or mitochondria targeted SOD mimetic mitoTEMPO. Angiotensin II‐induced hypertension led to impaired T cells respiration which was reversed by scavenging of mitochondrial H 2 O 2 . Despite impaired respiration, T cells from hypertensive mice synthesized more ATP compared to normotensive mice. Glycolysis was identified as the main source of ATP as indicated by increased lactate production. HPLC analysis showed higher glutamine uptake suggesting increased glutaminolysis. These metabolic changes facilitated T cell activity. Scavenging of mitochondrial superoxide prevented angiotensin II‐induced pro‐inflammatory cytokine production and ultimately hypertension in mice. Our data show that mitochondrial ROS‐dependent metabolic adaptation is necessary for T cell activation and their pro‐hypertensive responses. We suggest T cell mitochondrial ROS as a potential target for pharmacological intervention in hypertension. Grant Funding Source : Supported by National Institutes of Health grant R01HL094469.