En forskningsgrupp ledd av professor Karl Kunzelmann från PHI`s kund/partner Regensburg Uni har fått en forskningsrapport publicerad i ansedda Nature.
Professorn är f.ö. en produktiv forskare.Han ligger bakom 306 forskningsrapporter.
Contribution of TMEM16F to pyroptotic cell death
Pyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X7 is activated by the noncanonical inflammasome and contributes essentially to pyroptotic cell death. The Ca2+ activated phospholipid scramblase and ion channel TMEM16F has been shown earlier to control cellular effects downstream of purinergic P2X7 receptors that ultimately lead to cell death. As pyroptotic cell death is accompanied by an increases in intracellular Ca2+, we asked whether TMEM16F is activated during pyroptosis. The N-terminal cleavage product of gasdermin D (GD-N) is an executioner of pyroptosis by forming large plasma membrane pores. Expression of GD-N enhanced basal Ca2+ levels and induced cell death. We observed that GD-N induced cell death in HEK293 and HAP1 cells, which was depending on expression of endogenous TMEM16F. GD-N activated large whole cell currents that were suppressed by knockdown or inhibition of TMEM16F. The results suggest that whole cell currents induced by the pore forming domain of gasdermin-D, are at least in part due to activation of TMEM16F. Knockdown of other TMEM16 paralogues expressed in HAP1 cells suggest TMEM16F as a crucial element during pyroptosis and excluded a role of other TMEM16 proteins. Thus TMEM16F supports pyroptosis and other forms of inflammatory cell death such as ferroptosis. Its potent inhibition by tannic acid may be part of the anti-inflammatory effects of flavonoids.
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| Prof.Dr.med.Karl Kunzelmann |
Methods
Volume measurements using HoloMonitorTM
Cells were seeded in 35 mm dishes at a density of 300,000 cells/ dish. Cell morphology was observed after application of 10 µM ABT737 in IMDM medium containing 10% FBS or 100 ng/ml TNFα in OptiMEM for 24 h in a cell culture incubator (37 °C, humidified air, 5% CO2). The cell volume was calculated by quantitative phase microscopy in the HoloMonitorTM time-lapse cytometer (Phase Holographic imaging PHI, Lund, Sweden).
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| Cell morphology assessed by quantitative holographic phase microscopy. Scale bar indicates cell height. Mean + /− SEM (number of cells). #Significant inhibition when compared to parental cells (p < 0.05; unpaired t-test) |
Regensburg Uni figurerar nu 2 ggr på 2 veckor i en Springer Nature publikation.
Bloggen uppmärksammade i det sammanhanget deras första bidrag här.
Gemensamma nämnare för bägge bidragen är två. 1. Professor Kunzelmann 2. HoloMonitor.
1+2 = 6 vilket ger en intressant frågeställning som möjlighetspotential.
Utmaning
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Sammanfattningsvis har vi de senaste 20 dagarna fått se högkvalitativa artiklar i lika högkvalitativa kanaler.Branschens spejjarögon kan omöjligt ha undgått detta.Lägg till VD´s USA-äventyr.
Bloggen spekulerar nu friskt, men jag tippar att vi kommer få se händelseförlopp/resultat av något slag inom en inte alltför lång framtid.Triggade av senaste tidens händelser.
Er skribent i natten the99
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