scholarly journals Palmitate induces apoptotic cell death and inflammasome activation in human placental macrophages

2019 ◽  
Author(s):  
Lisa M. Rogers ◽  
Carlos H. Serezani ◽  
Alison J. Eastman ◽  
Alyssa H. Hasty ◽  
Linda Englund-Ögge ◽  
...  
Keyword(s):  
Cell Death ◽  
Metabolic Diseases ◽  
Apoptotic Cell ◽  
Interleukin 1 ◽  
Metabolic Stress ◽  
Apoptotic Cell Death ◽  
Inflammasome Activation ◽  
Placental Macrophages ◽  
The Impact ◽  
Placental Macrophage

AbstractIntroductionThere is an increasing prevalence of non-communicable diseases worldwide. Metabolic diseases such as obesity and gestational diabetes mellitus (GDM) increasingly affect women during pregnancy, which can harm pregnancy outcomes and the long-term health and wellbeing of exposed offspring. Both obesity and GDM have been associated with proinflammatory effects within the placenta, the critical organ governing fetal development.MethodsThe purpose of these studies was to model, in vitro, the effects of metabolic stress (high levels of glucose, insulin and saturated lipids) on placental macrophage biology, since these cells are the primary innate immune phagocyte within the placenta with roles in governing maternofetal immune tolerance and antimicrobial host defense. Macrophages were isolated from the villous core of term, human placentae delivered through nonlaboring, elective Cesarean sections and exposed to combinations of elevated glucose (30 mM), insulin (10 nM) and the saturated lipid palmitic acid (palmitate, 0.4 mM).ResultsWe found that palmitate alone induced the activation of the nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in placental macrophages, which was associated with increased interleukin 1 beta release and an increase in apoptotic cell death. Glucose and insulin neither provoked these effects nor augmented the impact of palmitate itself.DiscussionOur findings confirm an impact of saturated fat on placental macrophage immune activation and could be relevant to the impact of metabolic stress in vivo.

scholarly journals Palmitate induces apoptotic cell death and inflammasome activation in human placental macrophages

Placenta ◽  
2020 ◽  
Vol 90 ◽  
pp. 45-51 ◽  
Author(s):  
Lisa M. Rogers ◽  
Carlos H. Serezani ◽  
Alison J. Eastman ◽  
Alyssa H. Hasty ◽  
Linda Englund-Ögge ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Inflammasome Activation ◽  
Placental Macrophages

scholarly journals Dapagliflozin Alleviates Renal Fibrosis by Inhibiting RIP1-RIP3-MLKL-Mediated Necroinflammation in Unilateral Ureteral Obstruction

2022 ◽  
Vol 12 ◽  
Author(s):  
Mei Ying Xuan ◽  
Shang Guo Piao ◽  
Jun Ding ◽  
Qi Yan Nan ◽  
Mei Hua Piao ◽  
...  
Keyword(s):  
Cell Death ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Apoptotic Cell ◽  
Subsequent Development ◽  
Unilateral Ureteral Obstruction ◽  
Apoptotic Cell Death ◽  
Inflammasome Activation ◽  
Renal Tubular

Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, offers renoprotection in diabetes. However, potential for use in nondiabetic kidney disease remains unknown. Herein, we assessed whether dapagliflozin alleviates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and in vitro. After induction of UUO, rats were administered dapagliflozin daily for seven consecutive days. UUO induced significant renal tubular necrosis and overexpression of RIP1-RIP3-MLKL axis proteins; these coincided with NLRP3 inflammasome activation, and subsequent development of renal fibrosis. Oxidative stress caused by UUO is tightly associated with endoplasmic reticulum stress and mitochondrial dysfunction, leading to apoptotic cell death through Wnt3α/β-catenin/GSK-3β signaling; all of which were abolished by both dapagliflozin and specific RIP inhibitors (necrostatin-1 and GSK872). In H2O2-treated HK-2 cells, dapagliflozin and RIP inhibitors suppressed overexpression of RIP1-RIP3-MLKL proteins and pyroptosis-related cytokines, decreased intracellular reactive oxygen species production and apoptotic cell death, whereas cell viability was improved. Moreover, activated Wnt3α/β-catenin/GSK-3β signaling was inhibited by dapagliflozin and Wnt/β-catenin inhibitor ICG-001. Our findings suggest that dapagliflozin ameliorates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in UUO.

scholarly journals Pancracine, a Montanine-Type Amaryllidaceae Alkaloid, Inhibits Proliferation of A549 Lung Adenocarcinoma Cells and Induces Apoptotic Cell Death in MOLT-4 Leukemic Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7014
Author(s):  
Darja Koutová ◽  
Radim Havelek ◽  
Eva Peterová ◽  
Darina Muthná ◽  
Karel Královec ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
A549 Cells ◽  
Apoptotic Cell Death ◽  
Leukemic Cells ◽  
The Impact

Pancracine, a montanine-type Amaryllidaceae alkaloid (AA), is one of the most potent compounds among natural isoquinolines. In previous studies, pancracine exhibited cytotoxic activity against diverse human cancer cell lines in vitro. However, further insight into the molecular mechanisms that underlie the cytotoxic effect of pancracine have not been reported and remain unknown. To fill this void, the cell proliferation and viability of cancer cells was explored using the Trypan Blue assay or by using the xCELLigence system. The impact on the cell cycle was determined by flow cytometry. Apoptosis was evaluated by Annexin V/PI and by quantifying the activity of caspases (-3/7, -8, and -9). Proteins triggering growth arrest or apoptosis were detected by Western blotting. Pancracine has strong antiproliferative activity on A549 cells, lasting up to 96 h, and antiproliferative and cytotoxic effects on MOLT-4 cells. The apoptosis-inducing activity of pancracine in MOLT-4 cells was evidenced by the significantly higher activity of caspases. This was transmitted through the upregulation of p53 phosphorylated on Ser392, p38 MAPK phosphorylated on Thr180/Tyr182, and upregulation of p27. The pancracine treatment negatively altered the proliferation of A549 cells as a consequence of an increase in G1-phase accumulation, associated with the downregulation of Rb phosphorylated on Ser807/811 and with the concomitant upregulation of p27 and downregulation of Akt phosphorylated on Thr308. This was the first study to glean a deeper mechanistic understanding of pancracine activity in vitro. Perturbation of the cell cycle and induction of apoptotic cell death were considered key mechanisms of pancracine action.

scholarly journals Indication of an involvement of interleukin-1 beta converting enzyme- like protease in intramedullary apoptotic cell death in the bone marrow of patients with myelodysplastic syndromes

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2640-2647 ◽  
Author(s):  
SD Mundle ◽  
P Venugopal ◽  
JD Cartlidge ◽  
DV Pandav ◽  
L Broady-Robinson ◽  
...  
Keyword(s):  
Cell Death ◽  
Myelodysplastic Syndromes ◽  
Apoptotic Cell ◽  
Present Report ◽  
Interleukin 1 ◽  
Apoptotic Cell Death ◽  
Interleukin 1 Beta ◽  
Apoptotic Death ◽  
Healthy Donors

Our previous studies using in situ end labeling (ISEL) of fragmented DNA revealed extensive apoptotic cell death in the bone marrows (BM) of patients with myelodysplastic syndromes (MDS) involving both stromal and hematopoietic cells. In the present report we show greater synthesis of interleukin-1 beta (IL-1 beta) in 4 hour cultures of density separated BM aspirate mononuclear (BMAM) cells from MDS patients as compared to the cultures of normal BM from healthy donors or lymphoma patients (1.7 +/- 0.37 pg/10(5) cells, n = 29 v 0.42 +/- 0.24 pg/10(5) cells, n = 11, respectively, P = .049). Further, these amounts of IL-1 beta in MDS showed a significant correlation with the extent of apoptosis detected by ISEL in corresponding plastic embedded BM biopsies (r = .480, n = 30, P = .007). In contrast normal BMs did not show any correlation between the two (r = .091, n = 12, P = .779). No significant correlation was found between the amounts of IL-1 beta and % S-phase cells (labeling index; LI%) in MDS determined in BM biopsies using immunohistochemistry following in vivo infusions of iodo- and/or bromodeoxyuridine. Neither anti-IL-1 beta antibody nor IL-1 receptor antagonist blocked the apoptotic death of BMAM cells in 4 hour cultures (n = 5) determined by ISEL (apoptotic index; AI%), although the latter led to a dose-dependent accumulation of active IL-1 beta in the culture supernatants. On the other hand, a specific tetrapetide-aldehyde inhibitor of ICE significantly retarded the apoptotic death of BMAM cells at 1 mumol/L in 5/6 MDS cases studied (AI% = 2.99 +/- 0.30 in controls v 1.58 +/- 0.40 with ICE-inhibitor, P = .05) and also reduced the levels of active IL-1 beta synthesized (5.59 +/- 2.63 v 2.24 +/- 0.93 pg/10(6) cells, respectively). In normal cells, neither IL-1 blockers nor the ICE inhibitor showed any effect on the marginal increase in apoptosis observed in 4 hour cultures. Our data thus suggest a possible involvement of an ICE-like protease in the intramedullary apoptotic cell death in the BMs of MDS patients.

KIOM-79 prevents apoptotic cell death and AGEs accumulation in the retina of diabetic db/db mice

Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
YS Kim ◽  
EJ Sohn ◽  
HY Lee ◽  
CS Kim ◽  
YM Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death
Sign in / Sign up

Export Citation Format

Share Document