Premium
Mitochondrial superoxide in pro‐hypertensive T‐cell activation
Author(s) -
Nazarewicz Rafal R,
Dikalova Anna E,
Bikineyeva Alfiya T,
Harrison David G,
Dikalov Sergey I
Publication year - 2013
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.27.1_supplement.906.8
Subject(s) - sod2 , superoxide , mitochondrial ros , mitochondrion , superoxide dismutase , chemistry , microbiology and biotechnology , angiotensin ii , t cell , reactive oxygen species , immune system , endocrinology , medicine , biology , immunology , oxidative stress , biochemistry , receptor , enzyme
Activation of T‐cells and increased superoxide production are crucial in the development of hypertension (J Exp Med. 2007; 204:2449). Interestingly, depletion of mitochondrial superoxide dismutase (SOD2) increases hypertension while SOD2 overexpression blunts hypertension (Circ Res. 2010; 107:106). We hypothesized that mitochondrial superoxide plays an important role in T‐cell activation and pro‐hypertensive immune response. In order to test this hypothesis we investigated the effect of mitochondria targeted SOD2 mimetic mitoTEMPO and SOD2 expression (SOD2+/− or SOD2 overexpression) on T cell activation and pro‐hypertensive immune effect by adaptive transfer of T‐cells in RAG1 KO mice. Preliminary analysis of spleenocytes from hypertensive mice infused with angiotensin II showed decrease in mitochondrial membrane potential, increase in mitochondrial superoxide and cellular ATP that is consistent with attenuated mitochondrial function and activation of redox dependent glycolysis. Indeed, treatment of spleenocytes with mitochondria targeted antioxidant mitoTEMPO significantly blunted these changes. Since T‐cells are essential in pro‐hypertensive immune response, we isolated T‐cell fraction from spleenocytes and studied the role of mitochondrial superoxide in T‐cells proliferation and cytokine production. T‐cells isolated from hypertensive mice showed three fold increased cell proliferation and TNF‐α secretion which was blocked by treatment of T‐cells with mitoTEMPO. Therefore, this work suggets that mitochondrial superoxide is essential in T‐cells metabolic changes, activation and pro‐hypertensive immune response.