28 research outputs found
Lepton flavor violation decays in the topcolor-assisted technicolor model and the littlest Higgs model with parity
The new particles predicted by the topcolor-assisted technicolor ()
model and the littlest Higgs model with T-parity (called model) can
induce the lepton flavor violation () couplings at tree level or one loop
level, which might generate large contributions to some processes. Taking
into account the constraints of the experimental data on the relevant free
parameters, we calculate the branching ratios of the decay processes
with = , and
in the context of these two kinds of new physics models. We find
that the model and the model can indeed produce significant
contributions to some of these decay processes.Comment: 24 pages, 7 figure
Wnt signalling and cancer stem cells
[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060
Avaliação do potencial antioxidante frente à oxidação lipídica e da toxicidade preliminar do extrato e frações obtidas das frondes de Dicksonia sellowiana (Presl.) Hook
Targeting WNT, protein kinase B, and mitochondrial membrane integrity to foster cellular survival in the nervous system
Targeting essential cellular pathways that
determine neuronal and vascular survival can foster a
successful therapeutic platform for the treatment of a
wide variety of degenerative disorders in the central
nervous system. In particular, oxidative cellular injury
can precipitate several nervous system disorders that
may either be acute in nature, such as during cerebral
ischemia, or more progressive and chronic, such as
during Alzheimer disease. Apoptotic injury in the brain
proceeds through two distinct pathways that ultimately
result in the early externalization of membrane
phosphatidylserine (PS) residues and the late induction
of genomic DNA fragmentation. Degradation of DNA
may acutely impact cellular survival, while the exposure
of membrane PS residues can lead to microglial
phagocytosis of viable cells, cellular inflammation, and
thrombosis in the vascular system. Through either
independent or common pathways, the Wingless/Wnt
pathway and the serine-threonine kinase Akt serve
central roles in the maintenance of cellular integrity and
the prevention of the phagocytic disposal of cells
"tagged" by PS exposure. By selectively governing the
activity of specific downstream substrates that include
GSK-3ß, Bad, and ß-catenin, Wnt and Akt serve to
foster neuronal and vascular survival and block the
induction of programmed cell death. Novel to Akt is its
capacity to protect cells from phagocytosis through the
direct modulation of membrane PS exposure. Intimately
linked to the activation of Wnt signaling and Akt is the
maintenance of mitochondrial membrane potential and
the regulation of Bcl-xL, mitochondrial energy
metabolism, and cytochrome c release that can lead to
specific cysteine protease activation
The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury
Interest in the diverse biology of protein
tyrosine phosphatases that are encoded by more than 100
genes in the human genome continues to grow at an
accelerated pace. In particular, two cytoplasmic protein
tyrosine phosphatases composed of two Src homology 2
(SH2) NH2-terminal domains and a C-terminal proteintyrosine
phosphatase domain referred to as SHP-1 and
SHP-2 are known to govern a host of cellular functions.
SHP-1 and SHP-2 modulate progenitor cell
development, cellular growth, tissue inflammation, and
cellular chemotaxis, but more recently the role of SHP-1
and SHP-2 to directly control cell survival involving
oxidative stress pathways has come to light. SHP-1 and
SHP-2 are fundamental for the function of several
growth factor and metabolic pathways yielding far
reaching implications for disease pathways and disorders
such as diabetes, neurodegeneration, and cancer.
Although SHP-1 and SHP-2 can employ similar or
parallel cellular pathways, these proteins also clearly
exert opposing effects upon downstream cellular
cascades that affect early and late apoptotic programs.
SHP-1 and SHP-2 modulate cellular signals that involve
phosphatidylinositol 3-kinase, Akt, Janus kinase 2,
signal transducer and activator of transcription proteins,
mitogen-activating protein kinases, extracellular signalrelated
kinases, c-Jun-amino terminal kinases, and nuclear factor-kB. Our progressive understanding of the
impact of SHP-1 and SHP-2 upon multiple cellular
environments and organ systems should continue to
facilitate the targeted development of treatments for a
variety of disease entities
Metabotropic glutamate receptors promote neuronal and vascular plasticity through novel intracellular pathways
During the initial development and
maturation of an individual, the metabotropic glutamate
receptor (mGluR) system becomes a necessary
component for the critical integration of cellular function
and plasticity. In addition to the maintenance of cellular
physiology, the mGluR system plays a critical role
during acute and chronic degenerative disorders of the
central nervous system. By coupling to guanosinenucleotide-
binding proteins (G-proteins), the mGluR
system employs a broad range of signal transduction
systems to regulate cell survival and injury. More
commonly, it is the activation of specific mGluR
subtypes that can prevent programmed cell death (PCD)
consisting of two distinct pathways of genomic DNA
degradation and membrane phosphatidylserine (PS)
residue exposure. To offer this cellular protection,
mGluRs modulate a series of down-stream cellular
pathways that include protein kinases, mitochondrial
membrane potential, cysteine proteases, intracellular pH,
endonucleases, and mitogen activated protein kinases.
Prevention of cellular injury by the mGluR system is
directly applicable to clinical disability, since immediate
and delayed injury paradigms demonstrate the ability of
this system to reverse PCD in both neuronal and
vascular cell populations. Further understanding of the
intricate pathways that determine the protective nature of
the mGluR system will provide new therapeutic avenues
for the treatment of neurodegenerative disorders
Winding through the WNT pathway during cellular development and demise
In slightly over a period of twenty years, our
comprehension of the cellular and molecular
mechanisms that govern the Wnt signaling pathway
continue to unfold. The Wnt proteins were initially
implicated in viral carcinogenesis experiments
associated with mammary tumors, but since this period
investigations focusing on the Wnt pathways and their
transmembrane receptors termed Frizzled have been
advanced to demonstrate the critical nature of Wnt for
the development of a variety of cell populations as well
as the potential of the Wnt pathway to avert apoptotic
injury. In particular, Wnt signaling plays a significant
role in both the cardiovascular and nervous systems
during embryonic cell patterning, proliferation,
differentiation, and orientation. Furthermore, modulation
of Wnt signaling under specific cellular influences can
either promote or prevent the early and late stages of
apoptotic cellular injury in neurons, endothelial cells,
vascular smooth muscle cells, and cardiomyocytes. A
number of downstream signal transduction pathways can
mediate the biological response of the Wnt proteins that
include Dishevelled, ß-catenin, intracellular calcium,
protein kinase C, Akt, and glycogen synthase kinase-3ß.
Interestingly, these cellular cascades of the Wnt-Frizzled pathways can participate in several neurodegenerative,
vascular, and cardiac disorders and may be closely
integrated with the function of trophic factors.
Identification of the critical elements that modulate the
Wnt-Frizzled signaling pathway should continue to
unlock the potential of Wnt pathway for the
development of new therapeutic options against
neurodegenerative and vascular diseases
Activating Akt and the brain’s resources to drive cellular survival and prevent inflammatory injury
Protein kinase B, also known as Akt, is a
serine/threonine kinase and plays a critical role in the
modulation of cell development, growth, and survival.
Interestingly, Akt is ubiquitously expressed throughout
the body, but its expression in the nervous system is
substantially up-regulated during cellular stress,
suggesting a more expansive role for Akt in the nervous
system that may involve cellular protection. In this
regard, a body of recent work has identified a robust
capacity for Akt and its downstream substrates to foster
both neuronal and vascular survival during apoptotic
injury. Cell survival by Akt is driven by the modulation
of both intrinsic cellular pathways that oversee genomic
DNA integrity and extrinsic mechanisms that control
inflammatory microglial activation. A series of distinct
pathways are regulated by Akt that include the Forkhead
family of transcription factors, GSK-3ß, ß-catenin, c-
Jun, CREB, Bad, IKK, and p53. Culminating below
these substrates of Akt are the control of caspase
mediated pathways that promote genomic integrity as
well as prevent inflammatory cell demise. With further
levels of progress in defining the cellular role of Akt, the
attractiveness of Akt as a vital and broad cytoprotectant
for both neuronal and vascular cell populations should
continue to escalate