14 research outputs found
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Permeation Properties of Purified Pannexin 1 Channels in Proteoliposomes
Effect of Cardiopulmonary Bypass on SARS‐CoV‐2 Vaccination Antibody Levels
Background Adults undergoing heart surgery are particularly vulnerable to respiratory complications, including COVID‐19. Immunization can significantly reduce this risk; however, the effect of cardiopulmonary bypass (CPB) on immunization status is unknown. We sought to evaluate the effect of CPB on COVID‐19 vaccination antibody concentration after cardiac surgery. Methods and Results This prospective observational clinical trial evaluated adult participants undergoing cardiac surgery requiring CPB at a single institution. All participants received a full primary COVID‐19 vaccination series before CPB. SARS‐CoV‐2 spike protein‐specific antibody concentrations were measured before CPB (pre‐CPB measurement), 24 hours following CPB (postoperative day 1 measurement), and approximately 1 month following their procedure. Relationships between demographic or surgical variables and change in antibody concentration were assessed via linear regression. A total of 77 participants were enrolled in the study and underwent surgery. Among all participants, mean antibody concentration was significantly decreased on postoperative day 1, relative to pre‐CPB levels (−2091 AU/mL, P<0.001). Antibody concentration increased between postoperative day 1and 1 month post CPB measurement (2465 AU/mL, P=0.015). Importantly, no significant difference was observed between pre‐CPB and 1 month post CPB concentrations (P=0.983). Two participants (2.63%) developed symptomatic COVID‐19 pneumonia postoperatively; 1 case of postoperative COVID‐19 pneumonia resulted in mortality (1.3%). Conclusions COVID‐19 vaccine antibody concentrations were significantly reduced in the short‐term following CPB but returned to pre‐CPB levels within 1 month. One case of postoperative COVID 19 pneumonia‐specific mortality was observed. These findings suggest the need for heightened precautions in the perioperative period for cardiac surgery patients
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ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels
Pannexin 1 (Panx1) is a membrane channel implicated in numerous physiological and pathophysiological processes via its ability to support release of ATP and other cellular metabolites for local intercellular signaling. However, to date, there has been no direct demonstration of large molecule permeation via the Panx1 channel itself, and thus the permselectivity of Panx1 for different molecules remains unknown. To address this, we expressed, purified, and reconstituted Panx1 into proteoliposomes and demonstrated that channel activation by caspase cleavage yields a dye-permeable pore that favors flux of anionic, large-molecule permeants (up to ~1 kDa). Large cationic molecules can also permeate the channel, albeit at a much lower rate. We further show that Panx1 channels provide a molecular pathway for flux of ATP and other anionic (glutamate) and cationic signaling metabolites (spermidine). These results verify large molecule permeation directly through caspase-activated Panx1 channels that can support their many physiological roles
Recommended from our members
ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels
Pannexin 1 (Panx1) is a membrane channel implicated in numerous physiological and pathophysiological processes via its ability to support release of ATP and other cellular metabolites for local intercellular signaling. However, to date, there has been no direct demonstration of large molecule permeation via the Panx1 channel itself, and thus the permselectivity of Panx1 for different molecules remains unknown. To address this, we expressed, purified, and reconstituted Panx1 into proteoliposomes and demonstrated that channel activation by caspase cleavage yields a dye-permeable pore that favors flux of anionic, large-molecule permeants (up to ~1 kDa). Large cationic molecules can also permeate the channel, albeit at a much lower rate. We further show that Panx1 channels provide a molecular pathway for flux of ATP and other anionic (glutamate) and cationic signaling metabolites (spermidine). These results verify large molecule permeation directly through caspase-activated Panx1 channels that can support their many physiological roles