Necrosis

Question 1

necrosis

Answer 1

morphological characteristics of gain in cell volume, swelling of organelles, plasma membrane rupture, subsequent loss of intracellular contents

Question 2

necroptosis

Answer 2

type III PCD
morphological features of necrosis that is initiated by a programmed process involving “receptor-interacting protein kinase 1 and 3 aka RIP 1 and RIP 3
this process can be inhibited by necrostatin-1

Question 3

what induces necrosis?

Answer 3

SOMETIMES:

• after death ligand
• after toll receptor ligand
• by viral infections and exposure to double stranded RNA
• high levels of ROS
• DNA damage
• massive insult to plasma membrane
• treatment with calcium ionophores
• uncoupling of respiration and oxidative phosphorylation

Question 4

necrostatin-1

Answer 4

suppresses necrosis via death ligands

inhibits Receptor interacting protein kinase-1 RIP1

Question 5

RIP 3 is the 2nd key component needed for necroptosis

Answer 5

found in cytosol, forms a complex with RIP1, inhibited by necrostatin-1, cleaved and inativated by caspase8

Question 6

necrosome

Answer 6

a complex that mediates programmed necrosis

Question 7

necrosome mechanism

Answer 7

• formation of a plasma membrane receptor complex that activates NF signaling pathway providing cIAP is present which causes ubiquitination of RIP1
• complex is released into the cytosol and FADD and pro0caspase-8 associate with the complex
• if no caspase 8 inhibitor is present then procaspase 8 is converted to caspase 8 and caspase 8 cleaves both RIP 1 and RIP 3 and the result is APOPTOSIS
• if an inhibitor of procaspase 8 activation or caspase 8 activity is present then the RIP1/RIP3 complex becomes the necrosome and activates processes that result in necrosis

Question 8

macro-autophagy

Answer 8

type 2 programmed cell death

literally means to eat oneself

Question 9

types of autophagy

Answer 9

microautophagy
macroautophagy
chaperone-mediated

Question 10

induction of macroautophagy is mediated by

Answer 10

• nutrient deprivation
• energy depletion
• need to remove damaged proteins and organelles
• inhibiting normal suppressive signaling mechanism

Question 11

mechanistic aspects of autophagosome synthesis

Answer 11

• receipt of autophagic signal
• inhibition of mTOR
• activation of ULK1 complex
• release of Beclin-1 and activation of VPS34
• formation of phagophore nucleus
• formation of Atg12-Atg5/atg16 complex
• encasement of cargo
• closure of phagophore to form autophagosome
• fusion of autophagosome with lysosomes
• degradation of autophagosome and its cargo

Question 12

characteristics of cells undergoing autophagy

Answer 12

accumulation of cytosolic vacuoles with DOUBLE MEMBRANE
accumulation of LC3-II
accumulation of fluorescent puncta corresponding to either the aggregation of GFP-LC3 protein or staining with an antibody to LC3

Question 13

pro-survival function of macro-autophagy

Answer 13

to prevent apoptosis or necrosis from occurring
involved in everyday maintenance of homeostasis
induced as a response to stress/injury

Question 14

pro-death function of autophagy

Answer 14

cell death occurring in the absence of chromatin condensation, no caspase activation and accompanied by massive autophagic vacuolization of the cytoplasm
happens in very few cells

Question 15

resistance

Answer 15

insensitivity to an agent due to an irreversible process that generally has a genetic/epigenetic basis
-can be innate or acquired

Question 16

tolerance

Answer 16

a type of acquired resistance that is associated with a reduction in response to an agent that develops after repeated administration/exposure to agent
-can be reversible

Question 17

cross-resistance/cross tolerance

Answer 17

insensitivity to an agent that is distinct from the agent originally characterized as being resistant
usually structurally similar to the original agent or it shares a similar mechanism of action

Question 18

upregulated DNA repair pathways can cause resistance to

Answer 18

DNA-damaging agents

Question 19

in cancer one commonly observes

Answer 19

overexpression of anti-apoptotic proteins
reduced expression of pro-apoptotic proteins
activation of prosurvival signaling pathways