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Receptors in the regulation of suicidal erythrocyte death [Elektronische Ressource] / von Hasan Mahmud

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89 pages
Receptors in the Regulation of Suicidal Erythrocyte Death der Fakultät für Biologie der EBERHARD KARLS UNIVERSITÄT TÜBINGEN zur Erlangung des Grades eines Doktors der Naturwissenschaften von Hasan Mahmud aus Chuadanga, Bangladesch vorgelegte Dissertation 2009 Tag der mündlichen Prüfung: 23.10.2009 Dekan: Prof. Dr. Hanspeter A. Mallot 1. Berichterstatter: Prof. Dr. Florian Lang 2. Berichterstatter: Prof. Dr. Friedrich Götz Index I Receptors in the Regulation of Suicidal Erythrocyte Death 1. ABBREVIATIONS -------------------------------------------------------------------------------- 1 2. SUMMARY ----------------------------------------------------------------------------------------- 4 3. ZUSAMMENFASSUNG ------------------------------------------------------------------------- 6 4.
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der Fakultät für Biologie erEBERHARDKARLSUNIVERSITÄTT  zur Erlangung des Grades eines Dok der Naturwissenschaften         von Hasan Mahmud aus Chuadanga, Bangladesch                                                   vorgelegte                              Dissertation 2009
 
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                                              Tag der mündl                                       Dekan:Prof. Dr. Hanspeter A. Mallot   1. Berichterstatter:Prof. Dr. Florian L   2. Berichterstatter:Prof. Dr. Friedrich
 
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23.10.2009
 
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Götz 
IndexI                            
 
Receptors in the Regulation of Suicidal Erythrocyte Death
1. ABBREVIATIONS --------------------------------------------------------------- 1 -----------------
2. SUMMARY ----------------------------------------------------------------------------------------- 4  
3. ZUSAMMENFASSUNG ------------------------------------------------------------------------- 6
4. INTRODUCTION --------------------------------------------------------------------------------- 8
5.
 
Premise -------------------------------------------------------------------------------------------------- 8 
Composition of the erythrocyte membrane------------------------------------------------------ 8 
Erythrocyte Ion transport Pathway--------------------------------------------------------------- 9 
Apoptosis of nucleated cells --------------------------------- ------- 10 --------------------------------
Erythrocyte suicidal death ------------------------------------------------------------------------- 11 
Triggers of eryptosis ------------------------------------------------------------------------------- 11
Signaling involved in eryptosis ------------------------------------------------------------------- 12 Cl-channels: -------------------------------------------------------------------------------------- 12 Ca2+permeable cation channels --------------------------------------------------------------- 12 Oxidative stress and caspase activation triggers eryptosis--------------------------------- 13
Cycloxygenase activation, PGE2formation, and activation of Cation channels ----- 14 --Platelet activating factor stimulates sphingomyelinase ------------------------------------ 16
Physiological function of eryptosis -------------------------------------------------------------- 16
Lipopeptides ------------------------------------------------------------------------------------------- 17 
Characteristics--------------------------------------------------------------------------------------- 17
Pam3CSK4 ------------------------------------------------------------------------------------------ 18
TLR1-TLR2-Pam3CSK4 interaction ------------------------------------------------------------ 18
TLR1-TLR2-Pam3CSK4 signaling -------------------------------------------------------------- 19
Glutamate receptors --------------------------------------------------------------------------------- 21 
Overview--------------------------------------------------------------------------------------------- 21  
Ionic selectivity of glutamate receptors --------------------------------------------------------- 22
AMPA receptor agonists and antagonists ------------------------------------------------------- 22
Significance of AMPA receptors ----------------------------------------------------------------- 23
Leukotriene C4 --------------------------------------------------------------------------------------- 25 
Biosynthesis and metabolism of leukotriene --------------------------------------------------- 25
Leukotriene receptors ------------------------------------------------------------------------------ 27  
Biological effects of leukotrienes ---------------------------------------------------------------- 28
AIM OF THE STUDY --------------------------------------------------------------------------- 29
IndexI                            
6. MATERIALS AND METHODS--------------------------------------------------------------- 30
7.
Lipopeptides in the triggering of erythrocyte cell membrane scrambling --------------- 30 
Erythrocytes, solutions, and chemicals ---------------------------------------------------------- 30
FACS analysis of annexin V-binding and forward scatter ----------------------------------- 30 Measurement of intracellular Ca2+--------------------------------------------------------------- 31 Determination of ceramide formation ----------------------------------------------------------- 31
Statistics---------------------------------------------------------------------------------------------- 31
Modulation of erythrocyte survival by AMPA ------------------------------------------------ 32 
Erythrocyte, solution and chemicals ------------------------------------------------------------- 32
FACS analysis of PS exposure and forward scatter ------------------------------------------- 32 Measurement of intracellular Ca2+--------------------------------------------------------------- 33  
Patch clamp recordings ---------------------------------------------------------------------------- 33
Preparation of erythrocyte membrane and ghost ----------------------------------------------- 34  
Confocal microscopy------------------------------------------------------------------------------- 34
Statistics---------------------------------------------------------------------------------------------- 34
Participation of leukotriene C4 in eryptosis ---------------------------------------------------- 35 
Volunteers and solution---------------------------------------------------------------------------- 35
FACS analysis of PS exposure and forward scatter ------------------------------------------- 35 Measurement of intracellular Ca2+--------------------------------------------------------------- 35 Determination of leukotriene formation--------------------------------------------------------- 36
Erythrocyte membrane preparation -------------------------------------------------------------- 36
Immunoblotting ------------------------------------------------------------------------------------- 37
Confocal microscopy------------------------------------------------------------------------------- 37
Caspase 3 and 8 assays ------------------- ------------------------- 38 --------------------------------
Statistics---------------------------------------------------------------------------------------------- 38
RESULTS----------------------------------------------- 39 --------------------------------------------
Lipopeptides in the triggering of erythrocyte cell membrane scrambling ----------- 39 ----
Modulation of erythrocyte survival by AMPA ------------------------------------------------ 43 
Participation of leukotriene C4 in eryptosis ---------------------------------------------------- 50 
------------------------------------------8. DISCUSSION -------------------------------------------- 59
Lipopeptides in the triggering of erythrocyte cell membrane scrambling --------------- 59 
Modulation of erythrocyte survival by AMPA ------------------------------------------------ 61 
Participation of leukotriene C4 in eryptosis -- ---------------------------------- 63 ----------------
9. REFRENCES ----------------------------------------------- ------- 65 --------------------------------
 
IndexI                            
10. ACKNOWLEDGEMENTS ---------------------------------------------------------------------- 80
11. CURRICULUM VITAE -------------------------------------------------------------------------- 81
12. LIST OF PUBLICATIONS --------------------------------------------------------------------- 82
13. ACADEMIC TEACHERS------------------------------------------------------------------------ 84
 
 
 
 
FITC
FL
 
Abbreviations I
EIPA
EPO
FACS
FCS
1
Glutathion
GLUT
Glucose transporter
g gram
GluA
Glutamate receptor A
FSC
Forward scatter
EGTA
EDTA
COX
Ctr
DNQX
cysLT
h hour
GSH
Ethylisopropylamiloride
Ethylenediaminetetraacetic acid
6,7-dinitro-quinoxaline-2,3-dione
glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid
Cyclooxyginase 
Cysteinyl-leukotriene receptor
CNS
ATP
5-lipoxygenase activating protein
FLAP
Fluorescein isothyocyanate
Fluorescence channel
Fluorescence-activated cell sorting
Fetal calf serum
Control
Erythropoietin
Adenosine triphosphate
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic 
BSA Ca2+ 
CNQX
CMKRL1
  
1. ABBREVIATIONS   ACPA (R,S)-2-amino-3-(3
-carboxy-5-methyl-4-isoxazolyl)propionic acid
ALS
AMPA
6-cyano-7-nitroquinoxaline-2, 3-Dione
Central nervous system
Calcium
Chemoattractant-receptor-like-1
Akt
Bovine serum albumin
Amyotrophic Lateral Sclerosis
Protein Kinase B
Abbreviations I
Hb HCT HEPES HETE HPETE iGluRs IL iNOS IONO IRAK JAK K+ KCC
LT mM MyD88 + Na NBQX NF NHE NMDA NMDG NO
PAF PAMP PARP
PBS PGE2 PGN PLA PMSF PNQX PPAR PS
 
Hemogblobin Hematocrit 32 N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid Hydroxyeicosatetraenoic acids Hydroperoxyeicosatetraenoic acids Ionotropic glutamate receptors Interleukin Induciable nitric oxide synthase Ionomycin IL-1R-associated kinase Janus kinase Potassium K+/Cl- cotransporter Leukotriene Milimolar Myeloid differentiation factor-88
Sodium 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide Nuclear factor Na+/H+exchanger N-methyl-D-aspartate N-methyl-D-glucamine Nitric oxide Platelate activating factor Pathogen-associated molecular patterns Poly(ADP-ribose) polymerase 1 Phosphate-buffered saline Prostaglandin E2 Peptidoglycan Phospholipase A Phenyl methyl sulfonyl fluride 1,4,7,8,9,10-hexahydro-9-methyl- 6 nitro-pyrido[3,4-f]-quinoxaline-2,3-dione Peroxisome proliferators activated receptor Phosphatidylserine 
2
T
 
LR
 
t-BHP
 
S
SC
 
OD
S
S
M
S
EM
S
DS
S
AG
                                                                                                             
I
i
ons
Abbrevi
at
Staphylococcus aur
eus
S
 
Standard error of the mean
.aureus
ne, adenine, glucose
Sodium dodecyl sulfate
S
ali
l
l
Tol
 
de
i
Tert-butylhyd
roperox
Side scatt
er
S
ase
uper oxide dismut
S
phingomyeli
n
 
i
ke recept
or
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