Lecture 6

1.
What may follow DNA damage?
"Repair, misrepair, cell death"
2.
What does physical damage to DNA?
"Ionising radiation (x-rays, gamma-rays), ultraviolet radiation"
3.
What effect does ionising radiation have on DNA?
"Causes OH which, combined with ionising radiation, causes strand breaks,"
4.
How does ultraviolet radiation damage DNA?
"Adjacent pyrimidines (C, T) become linked, which contributes to cancer on misrepair. Excessive damage leads to death of keratinocytes (sunburn)."
5.
What is chemical damage that can occur to DNA?
"Aflatoxin B1 causes aflatoxicosis (liver injury) in high doses, or leads to G-T mutations and liver cancer"
6.
What are biological injuries to DNA?
B9 and B12 deficiency causes problems in DNA synthesis and repair and magaloblastic anaemia
7.
What are the phyical ways lipids are damaged?
"Crystals like silica, asbestos, cholesterol, MSU, hydroxyapatite puncture lysosomal membranes releasing hydrolytic enzymes. These activate inflammosomes generating damaging inflammation"
8.
What is chemical damage that occurs to lipids?
"Free radicals, ROS, and reactive nitrogen species damage lipids"
9.
What is biological damage that can occur to lipids?
Lipases (eg. from acute haemorrhagic pancreatitis) digest cell membranes
10.
What causes physical damage to proteins?
"Heat (high fever, heat stroke)"
11.
What are chemical damages to proteins?
"Glycation produces AGEs which inhibit protein function, generate ROS, bind to RAGE on vascular and inflammatory cells"
12.
What biologically damages proteins?
"Proteases (eg. collagen in arthritis, elastin in emphysema, laminin in cancer)"
13.
What are reversible effects on cells?
"Acute intracellular oedema, abnormal storage, adaptive responses"
14.
15.
How does abnormal storage occur?
"Accumulation of fat/glycogen due to increased concentration of FFAs, damaged hepatocytes unable to oxidise FAs"
16.
How may cells adapt to stress?
Transcription factors > response elements > transcription of protective protein genes
17.
What is the DNA damage response transcription factor?
"p53 > repair, cell cycle arrest, cell suicide"
18.
What is the antioxidant response transcription factor?
Nrf family induce genes encoding SOD1 and catalase
19.
What is the heat shock response transcription factor?
"Heat shock factors induce the expression of heat shock proteins (chaperones) that bind to denatured proteins, preventing aggregation, aid in renaturation, promote destruction of proteins that are too damaged"
20.
What are the hypoxia response transcription factors?
Hypoxia inducible factors
21.
What is the unfolded protein response transcription factor?
Chaperone synthesis transcription factor