David thompson course Flashcards
Name 3 ways by which the endothelium is antithrombotic
- heparan sulfate binds antithrombin
- thombomodulin binds thrombin, which is then unable to cleave fibrinogen. Thrombomodulin also activates protein C
- tissue factor pathway inhibitor inhibits factor X and tissue factor-factor VII , preventing thrombin generation
- neutral membrane charge on endothelium
the tubular system of a platelet is important for storing what (2 things)
Calcium and prostaglandin
what does delta platelet granules contain?
calcium
Gp11b-111a binds what?
fibrinogen
reduced ATP in case of ischemia reduces Na+ pumps, which increases CA2+ in the cells. Ca also increase due to Ca coming from mitochondria and ______
ER
tPA (tissue plasminigen activator) and ______ -> direct activation of fibrinolysis
Urokinase
Which is the only fibrillar type of collagen? Also a component of basement membrane (with laminin)
Type IV
what effect does reduced ph has on chromatin
clumping
name 3 antioxydant vitamins
vit A, C, E
name 2 enzymes that can degrade H2O2
gluthathione and catalase
which cells are involved in perforin granzyme apoptosis
NK and cytotoxic t cells are responsible for causing apoptosis in cells that are damaged, infected or tumoral
which are the 3 effector capsases
3, 6, 7
which proapoptotic proteions form the mitochondrial outer membrane permeabilization pore (MOMP)
Bax and bak
MPT vs MOMP, which one is necrosis vs apoptosis, and which one is in both inner and outer membrane?
MOMP = outer membrane, apoptosis. MPT= inner AND outer membrane, necrosis
what does the apoptosome activates (2 capsases 1 pathways)
capsase 9, then capase 3, SMAC/DIABLO
which proap[optotic protein is involved in the intrinsic AND extrinsic pathway?
Bid
transcytosis is upregulated by which protein?
VEGF
which selectin is stored in weibel palade bodies
p
what is NF-kappaB? (NF-KP)
important transcription factor of inflammation
what is the role of syndecan?
keep the glycocalyx on the endothelium
what are talin and vinculin
link between integrins and actin cytosqueleton
How do you call covalently modified dna
DNA adducts
What is the role of PARP-1
Slows down DNA replication process so that polymerase has time to fix mistakes. Seen with single strand break
If mistake is not fixed, PARP1 accumulates, activated p53 and cause apoptosis
Name something that can cause double stranded break
ROS, radiation
Name 3 proteins that are the major players ub homologous recombinatikn repair of DNA. Start with A, C and B
ATM/ART, CHK1/2, BRCA1/2
In case of a non homologous recombinasion repair, which 2 proteins are used to repair?
DNA-PK and Ligase IV
Which are the sensors in the dna damage response?
Ku, Rad, MRE/N
What is obligate haploinsufficiency
When one copy of a gene is not enough for normal phenotype
Name 3 non receptor tyrosine kinase (can move around in the cytosol and modify receptors)
Jak, Srec, Abl
What does PTEN does?
Blocks AKT pathway. PTEN is a tumor supressor
What does PI3K does to AKT?
Activates (phosphorylate)
TGFB uses which protein as signal transduction pathway
SMAD
SMADS are transcription factors except for one, which one?
Smad 4 (cofactor)
Remember that smad 6 and 7 are inhibitory
In tyrosine kinase receptor mutations, deletions are usually extracellular and cause hypo or hyperactivity?
Hyperactivity
What is the role of Famesyl membrane anchor
Keep RAS membrane associated
P16 and p21 are inhibitors of what
CDK inhibitors
Activated Rb is phosphorylated or not?
Unphosphorylated, therefore not binding E2F
Rb and p16 act on which CDK
CDK4/6 in G1
Which p__ acts through all steps of cell cyle?
P21
Which p__ mediates cell senescence
P16
What does SMAC/DIABLO does (2 things)
Activates caspases and neutralizes inhibitors of apoptosis proteins
What course of events happens when PTEN is absent in mutated cancer cells
Uncontrolled AKT activity-> AKT activates MDM2, MDM2 inactivates p53
What does RISC do?
Mediates the silencong of genes using ds-miRNA
What do Oct4, Sox2, c-Myc and KLF4 have in common?
They are transcription factors associated with embryonic stem cells
What does shelterin do?
Controls telomerase and dna repair enzymes access to telomere (protecting it)
What are the bodies where the telomerase is assembled and activated
Cajal bodies
production of more lactate vs pyruvate in tumor cells leads to _____ production. And why is methylation also increased in tumor cells?
Acetyl Coa production-> acetylated residues-> opens up histones
Serine production is increased in aerobic glycolysis
Which cytokine causes reduced MHC expression in cancer cells AND increases PDL1 expression
INFgamma
Which protein controls CTLA4 expression?
Foxp3
Which protein in papilloma virus causes p53 degradation
E6
E7 causes sequestering of RB in cytosol
Name 3 cytokines that increase vascular permeability
Il1, TNF, IFN gamma
Which TLR recognizes LPS
TLR4
E caderin plays a role in contact mediated growth inhibition and does something else (binds ___)
It binds and sequesters B-catenin, a signaling protein that functions in the WTN pathway (pathway that when activated causes proliferation)
What is the APC protein (what does it do?
Factor that negatively regulates the WNT pathway by forming a complex that degrades B catenin