Transcripts
DR. LINGWOOD:
Now, that's illustrated by the
fact that if you go through the literature and
look at the effects of verotoxin on cells, you
see a remarkable spectrum. Everybody, initially,
showed the toxin cells kills - inhibits protein
synthesis, and causes cytotoxicity. And it also
is a potent inducer of apoptosis, but I won't go
into that today, but apoptosis is a special
mechanism of cell killing.
But in some cells, for example,
mesangial cells, which are a component of the
glomerulus in the kidney, it doesn't kill the
cells, but it just prevents them from dividing.
In other cells at low concentrations, it actually
increases the biological activities of the cell,
it increases specific mRNA - messenger RNA -
levels in the cell, to increase their activity
and in these cells verotoxin induces the
production of cytokines. So while it inhibits
the protein synthesis, overall, it's actually
stimulating the protein synthesis of some very
specific proteins. These cytokines are
modulators of cell function.
It's also been shown that
binding of the toxin to the cell
surface can activate protein kinase which lay
under the cell surface, in the cytoplasm of the cell.
And the mechanism for that is totally
unknown. So that's a transmembrane signal, so
somehow binding on the outside it influences
activity on the inside of the membrane.
Now, I put question marks here,
and I've actually filled in one of these
questions marks as of last week. I've had some
collaborators looking at the bovine intestine
where presumably; there isn't any verotoxin
effect. Well, that's what has been presumed.
But in the bovine intestine,
actually, it's been shown that now the verotoxin
can increase the number of cells in the
epithelial cells - it causes hyperplastic
effects.
So it's quite the opposite in
the bovine intestine as to what we see in the
cell culture. So a whole plethora of
effects follows this single interaction that is --
a single interaction of the toxin with Gb3.
