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Sepsis remains a significant health care burden, with high morbidities and mortalities. Patients with sepsis often require general anesthesia for procedures and imaging studies. Knowing that anesthetic drugs can pose immunomodulatory effects, it would be critical to understand the impact of anesthetics on sepsis pathophysiology. The volatile anesthetic sevoflurane is a common general anesthetic derived from ether as a prototype. Using a murine sepsis model induced by cecal ligation and puncture surgery, we examined the impact of sevoflurane on sepsis outcome. Different from volatile anesthetic isoflurane, sevoflurane exposure significantly improved the outcome of septic mice. This was associated with less apoptosis in the spleen. Because splenic apoptosis was largely attributed to the apoptosis of neutrophils, we examined the effect of sevoflurane on FasL-induced neutrophil apoptosis. Sevoflurane exposure significantly attenuated apoptosis. Sevoflurane did not affect the binding of FasL to the extracellular domain of Fas receptor. Instead, analysis suggested that sevoflurane would bind to the interphase between Fas death domain (DD) and Fas-associated DD (FADD). The effect of sevoflurane on Fas DD-FADD interaction was examined using fluorescence resonance energy transfer (FRET). Sevoflurane attenuated FRET efficiency, indicating that sevoflurane hindered the interaction between Fas DD and FADD. The predicted sevoflurane binding site is known to play a significant role in Fas DD-FADD interaction, supporting our and apoptosis results.-Koutsogiannaki, S., Hou, L., Babazada, H., Okuno, T., Blazon-Brown, N., Soriano, S. G., Yokomizo, T., Yuki, K. The volatile anesthetic sevoflurane reduces neutrophil apoptosis Fas death domain-Fas-associated death domain interaction.
This article was published in the following journal.
Name: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
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A conserved protein interaction domain of the death domain superfamily that is structurally similar to the DEATH EFFECTOR DOMAIN and CASPASE RECRUITMENT DOMAIN. Death domains bind each other to form oligomers and occur on DEATH DOMAIN RECEPTORS, where they are required for APOPTOSIS signaling and non-apoptotic functions.
A homotypic protein interaction module of the death domain superfamily that is composed of a bundle of six alpha-helices. The death effector domain shares sequence and structural similarities with the DEATH DOMAIN and CASPASE RECRUITMENT DOMAIN. It occurs in many proteins with essential functions in APOPTOSIS.
A protein interaction domain of the death domain superfamily. It is characterized by a 6-helix bundle similar to those that occur in DEATH DOMAIN RECEPTORS. Pyrin domains are present in a variety of proteins, especially those that function in INFLAMMASOMES; AUTOPHAGY; and APOPTOSIS. They form homodimers or heterodimers with death domain proteins to facilitate the assembly of signaling complexes.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
Anesthesia is the loss of feeling or sensation in all or part of the body. It may result from damage to nerves or can be induced by an anesthetist (a medical professional) using anesthetics such as thiopental or propofol or sevoflurane during a surgical ...
Sepsis, septicaemia and blood poisoning
Septicaemia (another name for blood poisoning) refers to a bacterial infection of the blood, whereas sepsis can also be caused by viral or fungal infections. Sepsis is not just limited to the blood and can affect the whole body, including the organ...