Alzheimer’s
2007/7-11/24
Neurobiol Aging. 2007 Jun 21; [Epub ahead of print] Lin
CL, Chen
TF, Chiu
MJ, Way
TD, Lin
JK. Institute
of Biochemistry and Molecular Biology, Alzheimer's disease (AD) is the
most common neurodegenerative disease and is caused by an accumulation of Abeta plaque deposits in the brains. Evidence is
increasing that green tea flavonoids can protect
cells from Abeta-mediated neurotoxicity.
However, the underlying mechanism remains unclear. Here, we used a human
neuronal cell line MC65 conditional expression of an amyloid
precursor protein fragment (APP-C99) to investigate the protection
mechanism of epigallocatechin gallate
(EGCG), the main constituent of green tea. We demonstrated that treatment
with EGCG reduced the Abeta levels by enhancing
endogenous APP nonamyloidogenic proteolytic processing. Furthermore, EGCG also
decreased nuclear translocation of c-Abl and
blocked APP-C99-dependent GSK3beta activation, and these inhibitory effects
occurred through the interruption of c-Abl/Fe65 interaction. Our results
indicated that the neuroprotective action of EGCG
may take place through some mechanisms other than the promotion of APP nonamyloidogenic proteolysis, as was reported
previously. PMID: 17590240 [PubMed
- as supplied by publisher] Exp Dermatol. 2007 Aug;16(8):678-84. Hsu
S, Dickinson
D, Borke J, Walsh
DS, Wood
J, Qin H, Winger
J, Pearl
H, Schuster
G, Bollag WB. Department
of Oral Biology and Maxillofacial Pathology, Psoriasiform
lesions are characterized by hyperproliferation
and aberrant differentiation of epidermal keratinocytes,
accompanied by inflammation, leading to a disrupted skin barrier with an
abnormal stratum corneum. The expression and proteolytic processing of caspase
14, a member of the caspase family which is
associated with epithelial cell differentiation, planned cell death, and
barrier formation, is altered in psoriatic epidermis. We recently reported
that human psoriatic tissues lack normal expression of caspase
14 [J Dermatol Sci37 (2005) 61], and caspase 14 is induced by EGCG, a green tea polyphenol (GTP), in exponentially growing normal human
epidermal keratinocytes (NHEK) [J Pharmacol Exp Ther315 (2005) 805]. This suggests that GTPs may have beneficial effects on psoriasiform
lesions. The current study aimed to determine whether MAPK pathways are
required for GTP-induced caspase 14 expression in
NHEK and if GTPs can modulate the expression of
pathological markers in the psoriasiform lesions
that develop in the flaky skin mouse. The results indicate that the p38 and
JNK MAPK pathways are required for EGCG-induced expression of caspase 14 in NHEK. Importantly, topical application of
0.5% GTPs significantly reduced the symptoms of
epidermal pathology in the flaky skin mice, associated with efficient caspase 14 processing and reduction in proliferating
cell nuclear antigen levels. This suggests that GTP-activated pathways may
be potential targets for novel therapeutic approaches to the treatment of
some psoriasiform skin disorders. PMID: 17620095 [PubMed
- in process] Cancer Res.
2007 Jul 1;67(13):6493-501. Adachi
S, Nagao
T, Ingolfsson HI, Maxfield FR, Andersen
OS, Kopelovich L, Weinstein
IB. (-)-Epigallocatechin
gallate (EGCG), a major biologically active
constituent of green tea, inhibits activation of the epidermal growth
factor (EGF) receptor (EGFR) and downstream signaling pathways in several
types of human cancer cells, but the precise mechanism is not known.
Because several plasma membrane-associated receptor tyrosine kinases (RTK) including EGFR are localized in
detergent-insoluble ordered membrane domains, so-called "lipid
rafts," we examined whether the inhibitory effect of EGCG on
activation of the EGFR is associated with changes in membrane lipid order
in HT29 colon cancer cells. First, we did cold Triton X-100 solubility
assays. Phosphorylated (activated) EGFR was found
only in the Triton X-100-insoluble (lipid raft) fraction, whereas total
cellular EGFR was present in the Triton X-100-soluble fraction.
Pretreatment with EGCG inhibited the binding of Alexa
Fluor 488-labeled EGF to the cells and also
inhibited EGF-induced dimerization of the EGFR.
To examine possible effects of EGCG on membrane lipid organization, we
labeled the cells with the fluorescent lipid analogue 1, 1'-dihexadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate,
which preferentially incorporates into ordered membrane domains in cells
and found that subsequent treatment with EGCG caused a marked reduction in
the Triton X-100-resistant membrane fraction. Polyphenon
E, a mixture of green tea catechins, had a
similar effect but (-)-epicatechin (EC), the
biologically inactive compound, did not significantly alter the Triton
X-100 solubility properties of the membrane. Furthermore, we found that
EGCG but not EC caused dramatic changes in the function of bilayer-incorporated gramicidin channels. Taken
together, these findings suggest that EGCG inhibits the binding of EGF to
the EGFR and the subsequent dimerization and
activation of the EGFR by altering membrane organization. These effects may
also explain the ability of EGCG to inhibit activation of other
membrane-associated RTKs, and they may play a
critical role in the anticancer effects of this and related compounds. PMID: 17616711 [PubMed
- in process]
Epigallocatechin gallate (EGCG) suppresses beta-amyloid-induced
neurotoxicity through inhibiting c-Abl/FE65
nuclear translocation and GSK3beta activation.
Green tea polyphenol
induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model.
The inhibitory effect of (-)-epigallocatechin gallate on
activation of the epidermal growth factor receptor is associated with
altered lipid order in HT29 colon cancer cells.