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Role of Toll‐Like Receptor 4 Activation in Mitochondrial Respiration in Mouse Liver and Heart
Author(s) -
Pickering Brian,
Sharda Daniel
Publication year - 2015
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.29.1_supplement.954.8
Subject(s) - tlr4 , lipopolysaccharide , mitochondrion , respiration , chemistry , reactive oxygen species , receptor , respiratory system , reperfusion injury , ischemia , medicine , biochemistry , endocrinology , biology , anatomy
Ischemia reperfusion (I/R) injury results in activation of Toll‐like receptor 4 (TLR4) in cardiomyocytes, which contributes to tissue loss. Inhibiting TLR4 upon I/R results in improved recovery, as, paradoxically, does pretreatment with lipopolysaccharide (LPS), an activator of TLR4. However, it is unclear how TLR4 affects cardiomyoctes during LPS pretreatment or I/R injury. One clue may come from the recent discovery that TLR4 activation in macrophages enhances production of mitochondrial reactive oxygen species (mROS) due to perturbations in complex I of the electron transport chain (ETC). Therefore, we hypothesized that TLR4 activation in cardiomyocytes would decrease complex I respiration. Furthermore, we hypothesized that TLR4 activation would lead to mitochondrial uncoupling suggestive of mROS. In this study, mitochondria were isolated from hearts and livers of CD1 mice that had been pretreated for 1 hour i.p. with 1mg/kg LPS or vehicle control (PBS), and states 1‐4 of complexes I, II, and IV were analyzed using a Clarke‐type electrode for respiratory affects. Here we report that LPS did not affect complexes I ( p=0.38 for state 3), II ( p=0.37 ), and IV ( p=0.41 ) in the heart, or complex II in the liver ( p=0.36 ), indicating that LPS pretreatment does not modify ETC activity. Moreover, mitochondrial coupling displayed similar values for the respiratory control index (RCI) and respiratory control ratio (RCR) suggesting ROS production is unlikely to be affected by LPS pretreatment. Together, these data suggest that any pretreatment affects conferred by LPS at one hour are separate from the ETC, and remain a topic for future investigation. This work was funded by the Elbert Pence and Fanny Boyce Undergraduate Summer Research Grant.