Articles Blocks 1-2 Flashcards
Two major pathways of cell senescence
Replicative and stress-induced
What mediates the DNA damage response?
p53, p21, p16
Morphology of senescent cells
Enlarged, flattened, multinucleated, vacuolated
Accumulate lipofuscin
Increased beta-galactosidase
What part of the immune system do corals lack? What do they have that mammals don’t have?
Acquired; Amoebocytes are main cells of the innate immune system
Anoikis prevents
Adherent-independent cell growth
Relationship between anoikis and tumor invasion/metastasis
Resistance to anoikis=invasion and metastasis
What gives cells ability to resist anoikis?
EMT, antiapoptotic pathways (PI3K/Akt)
What has to be present for ferroptosis to occur?
Free iron in cell, lipid peroxides
What impairs glutathione peroxidase function?
GSH depletion, lack of cysteine
What causes the fenton reaction? What is the result?
free intracellular iron (ferrous iron) interacting with H2O2, forming ROS that cause lipid peroxidation (forms lipid peroxides)
When are NETs required?
Large microbial structures (fungal hyphae, bacterial aggregates)
What initiates NETosis?
LPS, flagella, immune complexes, complement products, DAMPs, cytokines, activated platelets
What causes proteolysis of histones and nucleosomes in NETs?
Neutrophil Elastase
NETosis pathway initiation
High levels of ROS activate PAD4, which mediates citrullination of histones, and dissolve cell membranes, so decondensed chromatin mixes with granule contents
What causes Parthanatos? What does this overactivate?
Extreme genomic stress with extensive DNA damage; PARP1
What phenotype are cells that undergo Mitochondrial Permeability Transition RCD; What triggers MPT RCD?
Necrotic; Severe oxidative stress and Ca overload
What does pyroptosis require? What is the outcome?
Caspase 1 (activated by inflammasome) and NFkappaB transcription via TLRs; inflammation
What is the effector of pyroptosis?
Gasdermin D (forms pore)
What is responsible for carrying out Lysosomal-Dependent Cell Death?
ROS causes lysosomal membrane permeabilization, which releases cathepsins
What is the result of lysosomal dependent cell death?
Either apoptosis through MOMP or necrosis (if severe LMP)
What is entosis? What triggers it?
Actomyosin-dependent cell in cell internalization; Epithelial cells lacking attachment to basement membrane or ECM
What is the hallmark of entosis that sets it apart from anoikis?
Cells drive their uptake into neighboring cells in endocytic membrane
What is the main morphological feature of entosis?
Bird’s eye cells, caused by accumulation of actomyosin chains and formation of cell in cell structures
Features of necroptosis
Pro-inflammatory
Caspase-independent
What is necroptosis dependent on? What inhibits it?
RIPK3; necrostatin, caspase 8 (cleaves RIPK)
What initiates necroptosis?
TNF-alpha binding death receptors
Possible outcomes of TNFalpha binding death receptor
RIPK ubiquitinated = NFkappaB survival
RIPK de-ubiquitinated = either Apoptosis if caspase 8, or necroptosis
Effector in necroptosis
MLKL
Possible outcome of necroptosis
PGAM5 causes membrane permeability transition pore formation
In atherosclerosis, how is the vasa vasorum affected? Major driver?
Increased in density; hypoxia–>VEGF
Difference between hepatic stellate cells and hepatic progenitor cells?
HSCs- in space of Disse, known as Ito cells, produce ECM and store vitamin A
HPCs- in Canals of Hering, known as oval cells, hepatocyte regeneration
How do HSCs cause fibrosis?
Differentiate into myofibroblasts that produce fibrogenic proteins
What activates hepatic stellate cells? Three fibrotic genes activated during this process? What holds these in inactive state when not stressed?
Unfolded protein response (ER stress); IRE1alpha, ATF6alpha, PERK; BiP (chaperone)
Inhibition of what molecule promotes atherogenesis?
NO
Membrane attack complex effect on nucleated cells
Less lytic than microbes due to cell defenses, initiates pro-inflammatory signaling
MAC induced effects on nucleated cells (
NLRP3 inflammasome and pyroptosis
Apoptosis
Necroptosis
NFkappaB mediated cell survival
What is the path for ICAM and VCAM expression on endothelial cells?
TNF, IL-1, Substance P stimulate GPCR, phospholipase converts PIP2 to DAG and IP3, which causes Ca influx from ER, which causes transcription of ICAM1 and VCAM1 via TF NFAT
What is the path for endothelial retraction?
Thrombin binds PAR1, which increases intracellular Ca (GPCR), which activates MLCK and MaMKIIdelta to cause actomyosin contraction, and activates annexin A2 to disassemble VE-Cadherin
Potent inducer of acute phase protein production
IL-6
Downregulated (negative) acute phase proteins
Albumin
Transferrin
Hepcidin’s role as acute phase protein
Bind transmembrane ferroportin to regulate transport of iron into plasma
Haptoglobin’s role as acute phase protein
Bind heme to prevent lipid peroxidation
Platelets express these adhesive molecules involved in NETosis (and their ligands/receptors on neutrophils)
P selectin - binds PSGL-1
Fibrinogen and integrin alphaIIBbetaIII - binds MAC1
GpIb and vWF binds MAC1
Platelets express these soluble molecules involved in NETosis (and their ligands/receptors on neutrophils)
HMGB-1 binds RAGE
PF4 and CCL5 (RANTES) chemokines bind GPCR
What mechanisms guide leukocyte-endothelial interactions
Cell number
Platelet bridging/chemokine signaling
Receptor density
Ligand affinity- clustering, conformational changes, post-translational mods
What is the purpose of In Situ Hybridization?
Localization of a specific (known) nucleic acid sequence using a complementary probe
