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Adaptation to Hypoxia > Hypoxia and gene expression > Flashcards

Hypoxia and gene expression Flashcards

1
Q

What are 6 diseases that have sustained hypoxia?

A

Altitude sickness
CO poisoning
Vascular disease
Stroke
Inflammation
Cancer

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2
Q

What is MDR1?

A

A chemotherapeutic resistant gene

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3
Q

Why are hypoxic cancer cells difficult to treat?

A

Far away from blood supply
Adaptive genes

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4
Q

What is the most common HIF target?

A

EPO

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5
Q

What is HIF?

A

Transcription factor that can regulate >200 genes associated with adaptation to hypoxia

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6
Q

What does the upregulation of HIF 1 alpha cause?

A

bind to promoter regions of target genes (adaptive genes)

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7
Q

What 4 things do adaptive genes trigger in hypoxia?

A

Glycolytic enzymes
Increased blood oxygenation
Increased vessel diameter
angiogensis

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8
Q

What are 3 genes that cause erthyropoesis?

A

EPO
Transferrin
Transferrin receptor

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9
Q

What are the 2 genes causing vasodilation?

A

iNOS
adrenomedullin

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10
Q

What 3 genes cause glycolysis?

A

GLUT 1 and 3
lactate dehydrogenase
phosphofructokinase

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11
Q

What 4 genes cause angiogenesis?

A

VEGF
VEGF-R
angiopoeitins
placental derived GF

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12
Q

What gene does HIF-1 switch in the mitochodria in hypoxia?

A

COX4-1 -> COX4-2 in hypoxia

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13
Q

What enzymes regulates HIF?

A

Hydroxylases at the level of accumulation & transactivation

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14
Q

How often is HIF mRNA made?

A

Constantly

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15
Q

What are the 2 types of hydroxylases?

A

PHD - adds OH to proline residues
FIH - adds OH to aspargine residues

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16
Q

What do the addition of OH by PHD cause?

A

Binding to VHL

17
Q

What does VHL promote binding of?

A

Ub chains - promote degradation of HIF

18
Q

What is FIH’s MoA in HIF activity in normoxia?

A

FIH uses oxygen as a substrate to asparagine to C terminal - CBP can no longer bind - no efficient transactivation of gene

19
Q

What are the 3 isoforms of PHD?

A

PHD 1,2 and 3

20
Q

What is the most important PHD for HIF?

21
Q

What are the 3 PHD substrates?

A

O2
Fe2+
ascorbate

22
Q

How many isoforms of FIH are there?

23
Q

What are the 3 substrates for FIH?

A

O2
Fe2+
ascorbate

24
Q

What 2 things does HIF1alpha require to become transcriptionally active?

A

HIF1beta and CBP

25
Q

What happens in VHL disease?

A

Cell thinks it’s hypoxic -> constituvely express HIF genes -> blood tumours

26
Q

Which residue is critical for VHL interaction?

A

Proline 564

27
Q

Where is proline 564 present in HIF1alpha?

A

Oxygen dependent degradation domain

28
Q

What happens if you stick ODD to another protein?

A

Confers oxygen sensitivity

Adaptation to Hypoxia (11 decks)

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