Search results for " signaling."

Increased Connexin 43 Expression as a Potential Mediator of the Neuroprotective Activity of the Corticotropin-Releasing Hormone

2009

CRH is a major central stress mediator, but also a potent neuroprotective effector. The mechanisms by which CRH mediates its neuroprotective actions are largely unknown. Here, we describe that the gap junction molecule connexin43 (Cx43) mediates neuroprotective effects of CRH toward experimentally induced oxidative stress. An enhanced gap junction communication has been reported to contribute to neuroprotection after neurotoxic insults. We show that CRH treatment up-regulates Cx43 expression and gap junctional communication in a CRH receptor-dependent manner in IMR32 neuroblastoma cells, primary astrocytes, and organotypic hippocampal slice cultures. MAPKs and protein kinase A-cAMP response…

How hypothalamic mitochondria translate the energy status of the boby

2017

IAPs: more than just inhibitors of apoptosis proteins.

2008

Inhibitors of apoptosis proteins (IAPs) are a conserved family of proteins identified in species ranging from virus, yeasts, nematodes, fishes, flies and mammals. The common structural feature is the presence of at least one Baculovirus IAP Repeat (BIR) domain. Hence, IAPs are also known as BIR-containing proteins (BIRCs). Most of them display anti-apoptotic properties when overexpressed. In drosophila, IAPs are sufficient and necessary to promote cell survival through a direct regulation of apoptotic proteases called caspases. In mammals, BIRC4/XIAP, the most studied IAP member can directly inhibit the activity of caspase-3, 7 and 9. However, this activity is not conserved in other IAPs an…

Targeting GSK3 and Associated Signaling Pathways Involved in Cancer

2020

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine (S/T) protein kinase. Although GSK-3 originally was identified to have functions in regulation of glycogen synthase, it was subsequently determined to have roles in multiple normal biochemical processes as well as various disease conditions. GSK-3 is sometimes referred to as a moonlighting protein due to the multiple substrates and processes which it controls. Frequently, when GSK-3 phosphorylates proteins, they are targeted for degradation. GSK-3 is often considered a component of the PI3K/PTEN/AKT/GSK-3/mTORC1 pathway as GSK-3 is frequently phosphorylated by AKT which regulates its inactivation. AKT is often active in human cancer a…

Theoretical Models of Industrial Espionage

2012

Dada la importancia del espionaje industrial en la realidad económica, el objetivo de la presente tesis es analizar teóricamente el comportamiento de las empresas a la hora de obtener información de sus competidores, para poder comprenderlo mejor y ver cuáles pueden ser sus consecuencias, ya que, aunque el espionaje industrial es una práctica muy extendida, pocos trabajos teóricos han tratado de analizarlo. Más concretamente, nuestro objetivo es analizar teóricamente el impacto del espionaje industrial sobre el comportamiento estratégico de las empresas en un contexto de disuasión de la entrada usando las herramientas propias de la Teoría de Juegos. En los modelos de la presente tesis se co…

B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma

2023

Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells’ signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL). Using bulk RNA and single cell analysis, we found five novel pathologic-independent clusters in DLBCL based on cells’ signaling. B-cell receptor (BCR) signaling was identified as the only enriched signal in DLBCL and pSS peripheral naive B-cells or salivary gland-infiltrated cells. The evaluation of the genes in association with …

Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging

2013

Recent genome-wide association studies have linked type-2 diabetes mellitus to a genomic region in chromosome 9p21 near the Ink4/Arf locus, which encodes tumor suppressors that are up-regulated in a variety of mammalian organs during aging. However, it is unclear whether the susceptibility to type-2 diabetes is associated with altered expression of the Ink4/Arf locus. In the present study, we investigated the role of Ink4/Arf in age-dependent alterations of insulin and glucose homeostasis using Super-Ink4/Arf mice which bear an extra copy of the entire Ink4/Arf locus. We find that, in contrast to age-matched wild-type controls, Super-Ink4/Arf mice do not develop glucose intolerance with agi…

Activation of NF-kappaB and IL-8 by yersinia enterocolitica invasin protein is conferred by engagement of rac1 and MAP kinase cascades.

2003

International audience; Yersinia enterocolitica triggers activation of the nuclear factor (NF)-kappaB and production of the proinflammatory chemokine interleukin (IL)-8 in intestinal epithelial cells. This activation is due to adhesion of the bacteria via their outer membrane protein invasin to the host cells. Using Clostridium difficile toxins that specifically inactivate small GTPases, and transfection of inhibitory proteins of the Rho-GTPases, we demonstrate that Rac1, but not Cdc42 or Rho, is required for activation of NF-kappaB by invasin. Invasin activated the mitogen activated protein kinases (MAPK) p38 and c-Jun N-terminal protein kinase (JNK) but not extracellular signal regulated …

Tiam1 as a Signaling Mediator of Nerve Growth Factor-Dependent Neurite Outgrowth

2010

Nerve Growth Factor (NGF)-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF) Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras- GTP), but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In add…

MTOR inhibitor-based combination therapies for pancreatic cancer

2018

Background: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. Methods: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance. Cross-species validation and pha…