B minocycline induced cell death involves calpain and

b. Minocycline-Induced Cell Death Involves Calpain and Caspase Activation.
c. Effects on pretreatment of cell with calpain inhibitor III or caspase inhibitors (z-VAD-fmk
and z-DEVD-fmk) was detected. With the presence of calpain and caspase inhibitor along

with higher concentration of minocycline, the cytotoxic effect of minocycline was found
to be decreased.
d. Only high concentration (30 mg/mL) of minocycline significantly decreased tumor
necrosis factor a (TNFa)-induced MMP-9 release.
e. Small concentration of minocycline could not reduce the TNF-aplha induced MMP-9 but
when the same concentration of MMP was loaded with liposome, there was sufficient
decrease in MMP-9 release and the effect on cell viability in both cases were found to be
same.
Limitations:
a. First, it is difficult to truly reconcile minocycline concentrations used in our cell culture
models with what happens in vivo.
b. A second caveat involves the mechanisms of endothelial cell death.
c. The data implicate both calpain and caspase but the precise molecular sequence of
these pathways are not fully known. Hence, combination therapies utilizing calpain or
caspase inhibitors plus minocycline are options that should be further explored.
d. Third, our experiments focus on cerebral endothelial cells because vascular MMPs
represent a critical target for stroke therapy.
e. However, whether liposome-encapsulated minocycline may also have important effects
in other brain cell types such as neurons and glia remain to be determined.
f. Finally, inflammation is a very complicated reaction to injury or disease in the brain.
g. Tumor necrosis factor a treatment in endothelial cell cultures is a very limited model
that attempts to mimic some of these inflammatory responses. Future studies to
validate these findings using in vivo stroke models are required.
QUESTION ASKED: