Search results for "death"

Characteristic ERK1/2 signaling dynamics distinguishes necroptosis from apoptosis

2021

International audience; ERK1/2 involvement in cell death remains unclear, although many studies have demonstrated the importance of ERK1/2 dynamics in determining cellular re- sponses. To untangle how ERK1/2 contributes to two cell death programs, we investigated ERK1/2 signaling dynamics during hFasL-induced apoptosis and TNF-induced necroptosis in L929 cells. We observed that ERK1/2 inhibition sensi- tizes cells to apoptosis while delaying necroptosis. By monitoring ERK1/2 activity by live-cell imaging using an improved ERK1/2 biosensor (EKAR4.0), we reported differential ERK1/2 signaling dynamics between cell survival, apoptosis, and nec- roptosis. We also decrypted a temporally shifted …

Cisplatin sensitivity is related to late DNA damage processing and checkpoint control rather than to the early DNA damage response

2008

The present study aimed at elucidating mechanisms dictating cell death triggered by cisplatin-induced DNA damage. We show that CL-V5B hamster mutant cells, a derivative of V79B, are hypersensitive to cisplatin-induced apoptotic death. CL-V5B cells are characterized by attenuated cisplatin-induced early (2-6 h) stress response, such as phosphorylation of stress-activated protein kinases (SAPK/JNK), ATM and Rad3-related (ATR) protein kinase, histone H2AX and checkpoint kinase-1 (Chk-1). Human FANCC cells also showed a reduced phosphorylation of H2AX and SAPK/JNK at early time point after cisplatin treatment. This was not the case for BRCA2-defective VC-8 hamster cells, indicating that the FA …

The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia

2018

Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat …

Vitamin E transport, membrane incorporation and cell metabolism: Is α-tocopherol in lipid rafts an oar in the lifeboat?

2010

International audience; Vitamin E is composed of closely related compounds, including tocopherols and tocotrienols. Studies of the last decade provide strong support for a specific role of alpha-tocopherol in cell signalling and the regulation of gene expression. It produces significant effects on inflammation, cell proliferation and apoptosis that are not shared by other vitamin E isomers with similar antioxidant properties. The different behaviours of vitamin E isomers might relate, at least in part, to the specific effects they exert at the plasma membrane. alpha-Tocopherol is not randomly distributed throughout the phospholipid bilayer of biological membranes, and as compared with other…

NO signaling in plant immunity: A tale of messengers

2015

International audience; Nitric oxide (NO) is a free radical gas involved in a myriad of plant physiological processes including immune responses. How NO mediates its biological effects in plant facing microbial pathogen attack is an unresolved question. Insights into the molecular mechanisms by which it propagates signals reveal the contribution of this simple gas in complex signaling pathways shared with reactive oxygen species (ROS) and the second messenger Ca2+. Understanding of the subtle cross-talks operating between these signals was greatly improved by the recent identification and the functional analysis of proteins regulated through S-nitrosylation, a major NO-dependent post-transl…

EFFECTS OF MCL-1 INHIBITION ON FOCAL ADHESION DYNAMICS IN BREAST CANCER MDA-MB-231 CELLS 

Type-2 histones deacetylases and cryptogein-induced cell death in tabacco

2011

Cryptogein, which is secreted by the oomycete Phytophthora cryptogea, is a proteinaceous elicitor of plant defense reactions that activates a set of signaling events leading to the hypersensitive response and to systemic acquired resistance. Although the early cytosolic signaling events induced by cryptogein are well described, the only nuclear events characterized to date are the variations in free calcium concentrations and defense-related gene expression. The characterization of the activation of cytosolic protein kinases, including WIPK and SIPK, by phosphorylation in response to cryptogein highlights the key-role played by posttranslational modifications in cryptogein-induced signaling…

Central and Peripheral Secondary Cell Death Processes after Transient Global Ischemia in Nonhuman Primate Cerebellum and Heart

2019

Cerebral ischemia and its pathological sequelae are responsible for severe neurological deficits generally attributed to the neural death within the infarcted tissue and adjacent regions. Distal brain regions, and even peripheral organs, may be subject to more subtle consequences of the primary ischemic event which can initiate parallel disease processes and promote comorbid symptomology. In order to characterize the susceptibility of cerebellar brain regions and the heart to transient global ischemia (TGI) in nonhuman primates (NHP), brain and heart tissues were harvested 6 months post-TGI injury. Immunostaining analysis with unbiased stereology revealed significant cell death in lobule II…

Onset of heart failure determines the hepatic cell death pattern.

2011

Background and rationale. Acute and chronic heart failure (HF) may affect the liver, but the underlying mechanisms that lead to progressive liver damage are poorly understood. The hepatic cytokeratin-18 (CK18) epitopes M65 and M30 have been reported to distinguish between overall (necrotic) and apoptotic cell death, respectively. We aimed to evaluate the predominant hepatic cell death pattern in acute vs. chronic heart failure and examined if these assays predict the course of the disease. Main results. In a prospective study comprising 21 patients with acute HF (AHF) and 18 patients with chronic HF (CHF) serum levels of M65 and M30 were assessed. Compared with CHF, M65 levels were signific…

Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives.

2009

This article is about Hsp10 and its intracellular and extracellular forms focusing on the relationship of the latter with Early Pregnancy Factor and on their roles in cancer and immunity. Cellular physiology and survival are finely regulated and depend on the correct functioning of the entire set of proteins. Misfolded or unfolded proteins can cause deleterious effects and even cell death. The chaperonins Hsp10 and Hsp60 act together inside the mitochondria to assist protein folding. Recent studies demonstrated that these proteins have other roles inside and outside the cell, either together or independently of each other. For example, Hsp10 was found increased in the cytosol of different t…