PMID- 29979630
OWN - NLM
STAT- MEDLINE
DCOM- 20190708
LR  - 20190708
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 33
IP  - 1
DP  - 2019 Jan
TI  - Down-regulation of acid sphingomyelinase and neutral sphingomyelinase-2 inversely 
      determines the cellular resistance to plasmalemmal injury by pore-forming toxins.
PG  - 275-285
LID - 10.1096/fj.201800033R [doi]
AB  - Bacterial pore-forming toxins compromise plasmalemmal integrity, leading to 
      Ca(2+) influx, leakage of the cytoplasm, and cell death. Such lesions can be 
      repaired by microvesicular shedding or by the endocytic uptake of the injured 
      membrane sites. Cells have at their disposal an entire toolbox of repair proteins 
      for the identification and elimination of membrane lesions. Sphingomyelinases 
      catalyze the breakdown of sphingomyelin into ceramide and phosphocholine. 
      Sphingomyelin is predominantly localized in the outer leaflet, where it is 
      hydrolyzed by acid sphingomyelinase (ASM) after lysosomal fusion with the plasma 
      membrane. The magnesium-dependent neutral sphingomyelinase (NSM)-2 is found at 
      the inner leaflet of the plasmalemma. Because either sphingomyelinase has been 
      ascribed a role in the cellular stress response, we investigated their role in 
      plasma membrane repair and cellular survival after treatment with the 
      pore-forming toxins listeriolysin O (LLO) or pneumolysin (PLY). Jurkat T cells, 
      in which ASM or NSM-2 was down-regulated [ASM knockdown (KD) or NSM-2 KD cells], 
      showed inverse reactions to toxin-induced membrane damage: ASM KD cells displayed 
      reduced toxin resistance, decreased viability, and defects in membrane repair. In 
      contrast, the down-regulation of NSM-2 led to an increase in viability and 
      enhanced plasmalemmal repair. Yet, in addition to the increased plasmalemmal 
      repair, the enhanced toxin resistance of NSM-2 KD cells also appeared to be 
      dependent on the activation of p38/MAPK, which was constitutively activated, 
      whereas in ASM KD cells, the p38/MAPK activation was constitutively 
      blunted.-Schoenauer, R., Larpin, Y., Babiychuk, E. B., Drucker, P., Babiychuk, V. 
      S., Avota, E., Schneider-Schaulies, S., Schumacher, F., Kleuser, B., Koffel, R., 
      Draeger, A. Down-regulation of acid sphingomyelinase and neutral 
      sphingomyelinase-2 inversely determines the cellular resistance to plasmalemmal 
      injury by pore-forming toxins.
FAU - Schoenauer, Roman
AU  - Schoenauer R
AD  - Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, 
      Switzerland.
FAU - Larpin, Yu
AU  - Larpin Y
AD  - Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, 
      Switzerland.
FAU - Babiychuk, Eduard B
AU  - Babiychuk EB
AD  - Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, 
      Switzerland.
FAU - Drucker, Patrick
AU  - Drucker P
AD  - Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, 
      Switzerland.
FAU - Babiychuk, Viktoriia S
AU  - Babiychuk VS
AD  - Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, 
      Switzerland.
FAU - Avota, Elita
AU  - Avota E
AD  - Institute of Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany; and.
FAU - Schneider-Schaulies, Sibylle
AU  - Schneider-Schaulies S
AD  - Institute of Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany; and.
FAU - Schumacher, Fabian
AU  - Schumacher F
AD  - Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
FAU - Kleuser, Burkhard
AU  - Kleuser B
AD  - Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
FAU - Koffel, Rene
AU  - Koffel R
AD  - Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, 
      Switzerland.
FAU - Draeger, Annette
AU  - Draeger A
AD  - Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, 
      Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180706
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Bacterial Proteins)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hemolysin Proteins)
RN  - 0 (Streptolysins)
RN  - 0 (plY protein, Streptococcus pneumoniae)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.- (acid sphingomyelinase-1)
RN  - EC 3.1.4.12 (SMPD3 protein, human)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
RN  - R06ZRQ1YX9 (hlyA protein, Listeria monocytogenes)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Bacterial Proteins/pharmacology
MH  - Bacterial Toxins/*pharmacology
MH  - Biological Transport
MH  - CRISPR-Cas Systems
MH  - Calcium/metabolism
MH  - Cell Membrane/chemistry/drug effects/*metabolism
MH  - Cell Survival
MH  - Cell-Derived Microparticles/chemistry/drug effects/metabolism
MH  - Heat-Shock Proteins/*pharmacology
MH  - Hemolysin Proteins/*pharmacology
MH  - Humans
MH  - Sphingomyelin Phosphodiesterase/*antagonists & inhibitors/genetics/metabolism
MH  - Streptolysins/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - annexins
OT  - bacterial toxins
OT  - blebbing
OT  - calcium
OT  - membrane repair
EDAT- 2018/07/07 06:00
MHDA- 2019/07/10 06:00
CRDT- 2018/07/07 06:00
PHST- 2018/07/07 06:00 [pubmed]
PHST- 2019/07/10 06:00 [medline]
PHST- 2018/07/07 06:00 [entrez]
AID - 10.1096/fj.201800033R [doi]
PST - ppublish
SO  - FASEB J. 2019 Jan;33(1):275-285. doi: 10.1096/fj.201800033R. Epub 2018 Jul 6.