The protective effect of propofol against TNF-α-induced apoptosis was mediated via inhibiting iNOS/NO production and maintaining intracellular Ca 2+ homeostasis in mouse hippocampal HT22 cells

2017 ◽  
Vol 91 ◽  
pp. 664-672 ◽  
Author(s):  
Zheng Xu ◽  
Yan Lu ◽  
Jiaqiang Wang ◽  
Xiaowei Ding ◽  
Jiawei Chen ◽  
...  
Keyword(s):  
Protective Effect ◽  
No Production ◽  
Ht22 Cells ◽  
Tnf Α ◽  
Intracellular Ca ◽  
Induced Apoptosis

Activation of cAMP-guanine exchange factor confers PKA-independent protection from hepatocyte apoptosis

2004 ◽  
Vol 287 (2) ◽  
pp. G334-G343 ◽  
Author(s):  
Kimberly A. Cullen ◽  
John McCool ◽  
M. Sawkat Anwer ◽  
Cynthia R. L. Webster
Keyword(s):  
Bile Acid ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Fas Ligand ◽  
Kinase Inhibitor ◽  
Pi3 Kinase ◽  
Akt Phosphorylation ◽  
Tnf Α ◽  
Induced Apoptosis

cAMP has previously been shown to promote cell survival in a variety of cell types, but the downstream signaling pathway(s) of this antiapoptotic effect is unclear. Thus the role of cAMP signaling through PKA and cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs) in cAMP's antiapoptotic action was investigated in the present study. cAMP's protective effect against bile acid-, Fas ligand-, and TNF-α-induced apoptosis in rat hepatocytes was largely unaffected by the selective PKA inhibitor, Rp-8-(4-chlorophenylthio)-cAMP (Rp-cAMP). In contrast, a novel cAMP analog, 8-(4-chlorophenylthio)-2′- O-methyl (CPT-2-Me)-cAMP, which activated cAMP-GEFs in hepatocytes without activating PKA, protected hepatocytes against apoptosis induced by bile acids, Fas ligand, and TNF-α. The role of cAMP-GEF and PKA on activation of Akt, a kinase implicated in cAMP survival signaling, was investigated. Inhibition of PKA with RP-cAMP had no effect on cAMP-mediated Akt phosphorylation, whereas CPT-2-Me-cAMP, which did not activate PKA, induced phosphatidylinositol 3-kinase (PI3-kinase)-dependent activation of Akt. Pretreatment of hepatocytes with the PI3-kinase inhibitor, Ly-294002, prevented CPT-2-Me-cAMP's protective effect against bile acid and Fas ligand, but not TNF-α-mediated apoptosis. Glucagon, CPT-cAMP, and CPT-2-Me-cAMP all activated Rap 1, a downstream effector of cAMP-GEF. These results suggest that a PKA-independent cAMP/cAMP-GEF/Rap pathway exists in hepatocytes and that activation of cAMP-GEFs promotes Akt phosphorylation and hepatocyte survival. Thus a cAMP/cAMP-GEF/Rap/PI3-kinase/Akt signaling pathway may confer protection against bile acid- and Fas-induced apoptosis in hepatocytes.

scholarly journals Anti-Vascular Inflammatory Effect of Ethanol Extract from Securinega suffruticosa in Human Umbilical Vein Endothelial Cells

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3448
Author(s):  
Byung Hyuk Han ◽  
Chun Ho Song ◽  
Jung Joo Yoon ◽  
Hye Yoom Kim ◽  
Chang Seob Seo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Protective Effect ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
No Production ◽  
Tnf Α ◽  
Umbilical Vein Endothelial Cells

Securiniga suffruticosa is known as a drug that has the effect of improving the blood circulation and relaxing muscles and tendons, thereby protects and strengthen kidney and spleen. Therefore, in this study, treatment of Securiniga suffruticosa showed protective effect of inhibiting the vascular inflammation in human umbilical vein endothelial cells (HUVECs) by inducing nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) coupling pathway. In this study, Securiniga suffruticosa suppressed TNF-α (Tumor necrosis factor–α) induced protein and mRNA levels of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and Interleukin-6 (IL-6). Pretreatment of HUVEC with Securiniga suffruticosa decreased the adhesion of HL-60 cells to Ox-LDL (Oxidized Low-Density-Lipoprotein)-induced HUVEC. Moreover, Securiniga suffruticosa inhibited TNF-α induced intracellular reactive oxygen species (ROS) production. Securiniga suffruticosa also inhibited phosphorylation of IκB-α in cytoplasm and translocation of NF-κB (Nuclear factor-kappa B) p65 to the nucleus. Securiniga suffruticosa increased NO production, as well increased the phosphorylation of eNOS and Akt (protein kinase B) which are related with NO production. In addition, Securiniga suffruticosa increased the protein expression of GTPCH (Guanosine triphosphate cyclohydrolase Ⅰ) and the production of BH4 in HUVEC which are related with eNOS coupling pathway. In conclusion, Securiniga suffruticosa has a protective effect against vascular inflammation and can be a potential therapeutic agent for early atherosclerosis.

Inflammatory cytokines (IL-1α, TNF-α) and LPS modulate the Ca2+signaling pathway in osteoblasts

1998 ◽  
Vol 274 (6) ◽  
pp. C1686-C1698 ◽  
Author(s):  
Vincent K. Tam ◽  
Sandra Schotland ◽  
Jacob Green
Keyword(s):  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
Neonatal Rat ◽  
Osteoblastic Cell ◽  
No Production ◽  
Osteoblastic Cell Line ◽  
Herbimycin A ◽  
Tnf Α ◽  
Intracellular Ca ◽  
Message System

Locally derived growth factors and cytokines in bone play a crucial role in the regulation of bone remodeling, i.e., bone formation and bone resorption processes. We studied the effect of interleukin (IL)-1α, tumor necrosis factor (TNF)-α, and Escherichia coli lipopolysaccharide (LPS) on the hormone-activated Ca2+message system in the osteoblastic cell line UMR-106 and in osteoblastic cultures derived from neonatal rat calvariae. In both cell preparations, IL-1α, TNF-α, and LPS did not alter basal intracellular Ca2+concentration ([Ca2+]i) but attenuated Ca2+transients evoked by parathyroid hormone (PTH) and PGE2in a dose (1–100 ng/ml)- and time (8–24 h)-dependent fashion. The cytokines modulated hormonally induced Ca2+influx (estimated by using Mn2+as a surrogate for Ca2+) as well as Ca2+mobilization from intracellular stores. The latter was linked to suppressed production of hormonally induced inositol 1,4,5-trisphosphate. The effect of cytokines on [Ca2+]iwas abolished by the tyrosine kinase inhibitor herbimycin A (50 ng/ml). The cytokine’s effect was, however, independent of nitric oxide (NO) production, since NO donors (sodium nitroprusside) as well as permeable cGMP analogs augment, rather than attenuate, hormonally induced Ca2+transients in osteoblasts. Given the stimulatory role of cytokines on NO production in osteoblasts, the disparate effects of cytokines and NO on the Ca2+signaling pathway may serve an autocrine/paracrine mechanism for modulating the effect of calciotropic hormones on bone metabolism.

scholarly journals NF-κB inactivation converts a hepatocyte cell line TNF-α response from proliferation to apoptosis

1998 ◽  
Vol 275 (4) ◽  
pp. C1058-C1066 ◽  
Author(s):  
Yang Xu ◽  
Shani Bialik ◽  
Brett E. Jones ◽  
Yuji Iimuro ◽  
Richard N. Kitsis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Nuclear Factor Κb ◽  
Hepatocyte Proliferation ◽  
No Production ◽  
Hepatocyte Cell Line ◽  
Tnf Α ◽  
Caspase 2 ◽  
Induced Apoptosis ◽  
Factor Α

Toxins convert the hepatocellular response to tumor necrosis factor-α (TNF-α) stimulation from proliferation to cell death, suggesting that hepatotoxins somehow sensitize hepatocytes to TNF-α toxicity. Because nuclear factor-κB (NF-κB) activation confers resistance to TNF-α cytotoxicity in nonhepatic cells, the possibility that toxin-induced sensitization to TNF-α killing results from inhibition of NF-κB-dependent gene expression was examined in the RALA rat hepatocyte cell line sensitized to TNF-α cytotoxicity by actinomycin D (ActD). ActD did not affect TNF-α-induced hepatocyte NF-κB activation but decreased NF-κB-dependent gene expression. Expression of an IκB superrepressor rendered RALA hepatocytes sensitive to TNF-α-induced apoptosis in the absence of ActD. Apoptosis was blocked by caspase inhibitors, and TNF-α treatment led to activation of caspase-2, caspase-3, and caspase-8 only when NF-κB activation was blocked. Although apoptosis was blocked by the NF-κB-dependent factor nitric oxide (NO), inhibition of endogenous NO production did not sensitize cells to TNF-α-induced cytotoxicity. Thus NF-κB activation is the critical intracellular signal that determines whether TNF-α stimulates hepatocyte proliferation or apoptosis. Although exogenous NO blocks RALA hepatocyte TNF-α cytotoxicity, endogenous production of NO is not the mechanism by which NF-κB activation inhibits this death pathway.

Manipulable Permeability of Nanogel Encapsulation on Cells Exerts Protective Effect against TNF-α-Induced Apoptosis

2018 ◽  
Vol 4 (8) ◽  
pp. 2825-2835 ◽  
Author(s):  
Wenyan Li ◽  
Guohui Zhang ◽  
Teng Guan ◽  
Xiaosha Zhang ◽  
Ali Khosrozadeh ◽  
...  
Keyword(s):  
Protective Effect ◽  
Tnf Α ◽  
Induced Apoptosis

Protective effect of ethyl-3-(3-dimethyl aminopropyl)urea dihydrochloride (EDU) against LPS-induced death in mice

2004 ◽  
Vol 53 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Tetsuya Matsumoto ◽  
Edward E.S. Nieuwenhuis ◽  
Ronald L. Cisneros ◽  
Begoña Ruiz-Perez ◽  
Keizo Yamaguchi ◽  
...  
Keyword(s):  
Protective Effect ◽  
Serum Levels ◽  
Treated Group ◽  
No Production ◽  
Raw 264.7 Macrophages ◽  
Tnf Α ◽  
Pre Treatment ◽  
Intra Abdominal Infection ◽  
Vehicle Treated Group

Evaluation of anti-adhesive gels and bioresorbable films in animal models of intra-abdominal infection has shown that a product of the cross-linking reaction between hyaluronic acid (HA) and CM-cellulose, 1-ethyl-3-(3-dimethyl aminopropyl)urea dihydrochloride (EDU), has immunomodulatory properties. The effects of EDU were evaluated by using an endotoxin-induced shock mouse model. Pre-treatment of mice with EDU (50 mg kg−1) in DMSO resulted in a significant reduction in mortality following injection of LPS, compared to vehicle (DMSO) pre-treatment alone. Serum levels of TNF-α, IL1β and IFN-γ in EDU-treated mice were significantly lower than those in vehicle-treated mice. Nitric oxide (NO) concentrations in the sera of mice after inoculation with LPS were significantly lower in the EDU-treated group than in the vehicle-treated group at various time-points. In contrast, EDU pre-treatment was associated with an enhanced IL10 response after LPS injection, compared to vehicle pre-treatment alone. In vitro studies revealed that IL10 production by RAW 264.7 macrophages, elicited by LPS, was increased significantly when EDU was added to the culture medium. These results suggest that the protective effect of EDU during LPS-induced shock in mice is the result of inhibition of proinflammatory cytokines and NO production and an enhanced IL10 response.

scholarly journals Protective Effect of Rosamultin against H2O2-Induced Oxidative Stress and Apoptosis in H9c2 Cardiomyocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Ling Zhang ◽  
Yang Liu ◽  
Jian Yu Li ◽  
Ling Zhi Li ◽  
Yong Liang Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Morphological Changes ◽  
Signal Pathways ◽  
Stress Injury ◽  
Pretreated Group ◽  
H9c2 Cardiomyocytes ◽  
Intracellular Ca ◽  
Mda Content ◽  
Induced Apoptosis

Rosamultin is one of the main active compounds isolated from Potentilla anserina L., which belongs to a triterpene compound. Few studies have examined the effect of rosamultin on oxidative stress and its molecular mechanism. The aim of this present study was to elucidate the protective effect of rosamultin on H2O2-induced oxidative damage and apoptosis in H9c2 cardiomyocytes and its mechanism. The results showed that the pretreatment of rosamultin not only increased cell viability but also reduced the release of LDH and CK. Rosamultin inhibited a H2O2-induced decrease in SOD, CAT, and GSH-Px activities and an increase in MDA content. Meanwhile, ROS level, intracellular (Ca2+) fluorescence intensity, and apoptosis rate in the rosamultin pretreated group were markedly decreased compared with the model group. Rosamultin pretreatment significantly reversed the morphological changes and attenuated H2O2-induced apoptosis. Western blot analysis showed that rosamultin enhanced the expression of Bcl-2 and pCryAB and downregulated the expression of Bax, Cyt-c, Caspase-3, and Caspase-9 expression. Additionally, rosamultin might activate PI3K/Akt signal pathways and CryAB relative factors. Therefore, we suggest that rosamultin could have the potential for treating H2O2-induced oxidative stress injury through its antioxidant and antiapoptosis effect.

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