FW: caspase-8 by flow cytometry

From: Rosson, Dan (RossonD@MLHS.ORG)
Date: Fri Jan 25 2002 - 15:46:01 EST


Cell Signaling Technology 978 867-2300 the sister Co of New England Biolabs
has just released an anti activated Caspase 8 antibody. They don't seem to
test their antibodies for flow, but both anti Caspase 3 and 8 are rated for
IHC, which is a good sign. I've tried the anti caspase 3 and it works for
flow.

Sincerely,

Dan Rosson

Dan Rosson Ph.D.
Lankenau Institute of Medical Research
100 Lancaster Ave.
Wynnewood, PA 19096


-----Original Message-----
From: DARZYNKIEWICZ ZBIGNIEW [mailto:DARZYNK@nymc.edu]
Sent: Thursday, January 24, 2002 5:16 PMSincerely,

To: cyto-inbox
Subject: caspase-8 by flow cytometry



Dr. Salinas inquires about caspase-8 assay by flow cytometry.

The most specific approach would be to use Ab that reacts with the activated
form of caspase-8 but not with pro-caspase-8. Although large number of
caspase-8 Ab are commercially available, I have not seen yet the published
data showing the use of Ab to detect activation of caspase-8 by flow
cytometry. Abs against activated caspase-3 and -9 are listed in some
catalogues.

Alternative approach is to use either caspase specific fluorogenic substrate
or fluorochrome-labeled inhibitor (FLICA), with the LEDT peptide sequence.
We observed, however, that specificity of  most substrates and inhibitors is
not as great as advertised. Perhaps this is a reflection of the fact that to
label the enzyme in live cells the substrates or inhibitore are being used
at two to three orders of magnitude higher concentration than their binding
association (Km). Because of that we do not know what is their effective
local concentration within the cells at the site of activated caspase.
Neither we know whether Km (and peptide specificity) of a particular caspase
in situ is the same as of the isolated enzyme (which served to test the
specificity). One has to be careful, therefore, drawing conclusions about
specificity of such reagents.

Zbigniew Darzynkiewicz
Brander Cancer Research Institute
New York Medical College
19 Bradhurst Ave.
Hawthorne, NY 10532
tel: 914-347-2801
fax: 914-347-2804
http://www.geocities.com/z_darzynkiewicz



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