Search results for "p38"

Activation of microglia synergistically enhances neurodegeneration caused by MPP+ in human SH-SY5Y cells

2019

While MPP+ may not directly activate microglia, the initial neuronal damage inflicted by the toxin may trigger microglia, possibly leading to synergistic pro-apoptotic interaction between neuro-inflammation and toxin-induced neurotoxicity, which may further aggravate neurodegeneration. However, what molecular targets are synergistically up or downregulated during this interaction is not well understood. Here, we addressed this by co-culturing fully differentiated human SH-SY5Y cells treated with parkinsonian toxin 1-Methyl-4-phenylpyridinium (MPP+), with endotoxin-activated microglial cell line EOC 20 to determine how this interaction affects pro-apoptotic (p38, JNK, and bax:bcl2 ratios) an…

Cytotoxicity ofSalvia miltiorrhizaAgainst Multidrug-Resistant Cancer Cells

2016

Salvia miltiorrhiza Bunge (Lamiaceae) is a well-known Chinese herb that possesses numerous therapeutic activities, including anticancer effects. In this study, the cytotoxicity and the biological mechanisms of S. miltiorrhiza (SM) root extract on diverse resistant and sensitive cancer cell lines were investigated. CEM/ADR5000 cells were 1.68-fold resistant to CCRF-CEM cells, while HCT116 (p53[Formula: see text] and U87.MG[Formula: see text]EGFR cells were hypersensitive (collateral sensitive) compared to their parental cells. SM root extract stimulated ROS generation, cell cycle S phase arrest and apoptosis. The induction of the intrinsic apoptotic pathway was validated by increased cleavag…

HSP60 activity on human bronchial epithelial cells

2017

HSP60 has been implicated in chronic inflammatory disease pathogenesis, including chronic obstructive pulmonary disease (COPD), but the mechanisms by which this chaperonin would act are poorly understood. A number of studies suggest a role for extracellular HSP60, since it can be secreted from cells and bind Toll-like receptors; however, the effects of this stimulation have never been extensively studied. We investigated the effects (pro- or anti-inflammatory) of HSP60 in human bronchial epithelial cells (16-HBE) alone and in comparison with oxidative, inflammatory, or bacterial challenges. 16-HBE cells were cultured for 1–4 h in the absence or presence of HSP60, H2O2, lipopolysaccharide (…

Wip1 phosphatase: between p53 and MAPK kinases pathways.

2016

IF 5.008; International audience; Cells undergoing oncogenic transformation frequently inactivate tumor suppressor pathways that could prevent their uncontrolled growth. Among those pathways p53 and p38MAPK pathways play a critical role in regulation of cell cycle, senescence and cell death in response to activation of oncogenes, stress and DNA damage. Consequently, these two pathways are important in determining the sensitivity of tumor cells to anti-cancer treatment. Wild type p53-induced phosphatase, Wip1, is involved in governance of both pathways. Recently, strategies directed to manipulation with Wip1 activity proposed to advance current day anticancer treatment and novel chemical com…

Multifaceted Mechanisms of WY-14643 to Stabilize the Blood-Brain Barrier in a Model of Traumatic Brain Injury

2017

The blood-brain barrier (BBB) is damaged during ischemic insults such as traumatic brain injury or stroke. This contributes to vasogenic edema formation and deteriorate disease outcomes. Enormous efforts are pursued to understand underlying mechanisms of ischemic insults and develop novel therapeutic strategies. In the present study the effects of PPARα agonist WY-14643 were investigated to prevent BBB breakdown and reduce edema formation. WY-14643 inhibited barrier damage in a mouse BBB in vitro model of traumatic brain injury based on oxygen/glucose deprivation in a concentration dependent manner. This was linked to changes of the localization of tight junction proteins. Furthermore, WY-1…

Role of Adrenomedullin in LSP-mediated lung injury

2014

Posttranslationally modified proteins as mediators of sustained intestinal inflammation.

2006

Oxidative and carbonyl stress leads to generation of N(epsilon)-carboxymethyllysine-modified proteins (CML-mps), which are known to bind the receptor for advanced glycation end products (RAGE) and induce nuclear factor (NF)-kappaB-dependent proinflammatory gene expression. To determine the impact of CML-mps in vivo, RAGE-dependent sustained NF-kappaB activation was studied in resection gut specimens from patients with inflammatory bowel disease. Inflamed gut biopsy tissue demonstrated a significant up-regulation of RAGE and increased NF-kappaB activation. Protein extracts from the inflamed zones, but not from noninflamed resection borders, caused perpetuated NF-kappaB activation in cultured…

Repeated muscle biopsies through a single skin incision do not elicit muscle signaling, but IL-6 mRNA and STAT3 phosphorylation increase in injured m…

2011

To determine if muscle biopsies can be repeated using a single small (5–6 mm) skin incision without inducing immediate MAPK activation or inflammation in the noninjured areas, the phosphorylation of ERK1/2, p38-MAPK, c-Jun NH2-terminal kinases (JNKs), IκBα, IKKα, and signal transducer and activator of transcription 3 (STAT3) was examined concurrent with IL-6 mRNA in six muscle biopsies obtained from the vastus lateralis of five men. Four biopsies were obtained through the same incision (5–6 mm) from the right leg (taken at 0, 30, 123, and 126 min) and another two each from new incisions performed in the left leg (at 31 and 120 min), while the subjects rested supine. The first three biopsie…

Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training

2014

This study investigated the effects of vitamin C and E supplementation on acute responses and adaptations to strength training. Thirty-two recreationally strength-trained men and women were randomly allocated to receive a vitamin C and E supplement (1000 mg day(-1) and 235 mg day(-1), respectively), or a placebo, for 10 weeks. During this period the participants' training involved heavy-load resistance exercise four times per week. Muscle biopsies from m. vastus lateralis were collected, and 1 repetition maximum (1RM) and maximal isometric voluntary contraction force, body composition (dual-energy X-ray absorptiometry), and muscle cross-sectional area (magnetic resonance imaging) were measu…

Lipocalin-2 Regulates Hippocampal Microglial Activation in Poststroke Depression

2021

Background and Purpose: Microglia play important role in poststroke depression (PSD), however, the exact mechanism was still unclear. The purpose of the study was to study the mechanism of microglial activation in PSD.Methods: 24 rats were randomly divided into three groups: the PSD group (n = 10), the poststroke (PS) group (n = 7), and the sham group (n = 7). Primary hippocampal microglia were isolated and cultured, and recombined LCN2 protein was used to stimulate the cultured microglia. The protein expression of Iba1, P38 MAPK and PP38 MAPK was analyzed by western blotting; the LCN2 expression was measured by RT-qPCR, the serum LCN2 level and the NO level were analyzed by ELISA.Results: …