Zinc

Question 1

Outline the features of metallothionein.

Answer 1

60-63 amino acids

Binds 1B and 2B metals with high affinity (Kd is 10^11 for Zn and 10^19 for Cu(I))

Organised metals in 2 clusters

Question 2

How can Zn signals be generated?

Answer 2

Gating Zn channels

Release of Zn from proteins by oxidation or nitrosylation of metal thiolate bonds.

Question 3

What results from Zn permeating into the post synaptic neurone through a uniporter?

Answer 3

Mt membrane potential falls –> increased ROS and RNS.

Inhibits complex III or complex I and aKGDH.

MPTP also shown to open and release CytC and AIF.

Question 4

How does IL-8 link to Zinc and where is it expressed in humans?

Answer 4

Important chemotactic cytokine in lung and expression regulated by ERK, JNK and p38 pathways.

Increases in response to ambient particulate matter and PM associated zinc.

Elevated levels –> bronchoconstriction, oedema and neutrophilia.

Question 5

How do we know that G6PD and MT are driven by cytosolic zinc-mediated induction of MTF-1?

Answer 5

Treat cells with H2O2 - increases the proteins but below baseline when add TPEN (Chung et al)

Hogstrand et al - add zinc to cells, MT expression shoots up but knocking down MTF-1 –> response blunted.