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

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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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• Gesundheit

Informations

• Publié par: eberhard_karls_universitat_tubingen
• Publié le: 01 janvier 2009
• Nombre de lectures: 71
• Langue: English
• Poids de l'ouvrage: 1 Mo

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der Fakultät für Biologie erE BERHARD K ARLS U NIVERSITÄT T   zur Erlangung des Grades eines Dok der Naturwissenschaften                 von Hasan Mahmud aus Chuadanga, Bangladesch                                                    vorgelegte                              Dissertation 2009

 

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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 Ca 2+ permeable cation channels --------------------------------------------------------------- 12 Oxidative stress and caspase activation triggers eryptosis--------------------------------- 13

Cycloxygenase activation, PGE 2 formation, 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 Ca 2+ --------------------------------------------------------------- 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 Ca 2+ --------------------------------------------------------------- 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 Ca 2+ --------------------------------------------------------------- 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 Ca 2+  

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 E 2   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

 

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ke recept

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