scholarly journals Pentose Phosphate Pathway Regulates Tolerogenic Apoptotic Cell Clearance and Immune Tolerance

2022 ◽  
Vol 12 ◽  
Author(s):  
Dan He ◽  
Qiangdongzi Mao ◽  
Jialin Jia ◽  
Zhiyu Wang ◽  
Yu Liu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Immune Tolerance ◽  
Lupus Erythematosus ◽  
Pentose Phosphate Pathway ◽  
Apoptotic Cell ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Macrophage Phagocytosis ◽  
Cell Clearance ◽  
Underlying Mechanisms

The efficient removal of apoptotic cells (ACs), a process termed as efferocytosis, is essential for immune homeostasis. While recent work has established an important interplay between efferocytosis and cellular metabolic changing, underlying mechanisms remain poorly known. Here, we discovered that pentose phosphate pathway (PPP) regulates tolerogenic ACs clearance and immune tolerance. ACs decreased levels of PPP-related genes and metabolites in macrophages. AG1, the agonist of PPP, increased the activity of PPP but greatly reduced macrophage phagocytosis of ACs and enhanced the inflammatory response during efferocytosis. miR-323-5p regulated the expression of PPP-related genes and its levels increased during efferocytosis. miR-323-5p inhibitor greatly promoted levels of PPP-related genes, reduced the macrophage phagocytosis of ACs, and increased inflammatory response during efferocytosis, suggesting that miR-323-5p was essential in regulating PPP activity and ACs clearance in macrophages. Correspondingly, the PPP agonist AG1 exacerbated the lupus-like symptoms in the AC-induced systemic lupus erythematosus (SLE) model. Our study reveals that regulating PPP-dependent metabolic reprogramming is critical for tolerogenic ACs phagocytosis and immune tolerance.

Effects of insulin, glucocorticoids and thyroid hormones on the activities of key enzymes of glycolysis, glutaminolysis, the pentose-phosphate pathway and the Krebs cycle in rat macrophages

1992 ◽  
Vol 135 (2) ◽  
pp. 213-219 ◽  
Author(s):  
L. F. B. P. Costa Rosa ◽  
Y. Cury ◽  
R. Curi
Keyword(s):  
Thyroid Hormones ◽  
Pentose Phosphate Pathway ◽  
Culture Medium ◽  
Citrate Synthase ◽  
Inflammatory Responses ◽  
Krebs Cycle ◽  
Pentose Phosphate ◽  
Macrophage Phagocytosis ◽  
And Function ◽  
Glucose 6 Phosphate Dehydrogenase

ABSTRACT In the present study the effects of insulin, glucocorticoids and thyroid hormones on macrophage metabolism and function were investigated. The maximum activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase and citrate synthase were determined in macrophages obtained from hormonetreated rats and those cultured for a period of 48 h in the presence of hormones. Macrophage phagocytosis was markedly inhibited by dexamethasone and thyroid hormones, remaining unchanged when insulin was added to the culture medium, however. The changes in the enzyme activities caused by hormone treatments of the rats were very similar to those found in culture. Insulin enhanced citrate synthase and hexokinase activities and diminished those of glutaminase and glucose-6-phosphate dehydrogenase. Dexamethasone had a similar effect except on glucose6-phosphate dehydrogenase. The addition of thyroid hormones to the culture medium raised the activities of glutaminase and hexokinase and reduced that of citrate synthase. The results presented support the suggestion that the effects of insulin, glucocorticoids and thyroid hormones on immune and inflammatory responses could well be mediated through changes in macrophage metabolism.. Journal of Endocrinology (1992) 135, 213–219

scholarly journals Apoptotic cell clearance in systemic lupus erythematosus: II. Role of ?2-glycoprotein I

1998 ◽  
Vol 41 (2) ◽  
pp. 215-223 ◽  
Author(s):  
Angelo A. Manfredi ◽  
Patrizia Rovere ◽  
Silvia Heltai ◽  
Giacomo Galati ◽  
Gaia Nebbia ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Apoptotic Cell ◽  
Systemic Lupus ◽  
Apoptotic Cell Clearance ◽  
Glycoprotein I ◽  
Cell Clearance

scholarly journals Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2731
Author(s):  
Andjelika Kalezic ◽  
Mirjana Udicki ◽  
Biljana Srdic Galic ◽  
Marija Aleksic ◽  
Aleksandra Korac ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Pentose Phosphate Pathway ◽  
Warburg Effect ◽  
Normal Weight ◽  
Pentose Phosphate ◽  
Breast Cancer Tissue ◽  
Metabolic Reprogramming ◽  
Cancer Tissue

Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5′-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1—PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase—G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue.

scholarly journals MicroRNA-Mediated Metabolic Reprograming in Renal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1825 ◽  
Author(s):  
Bogusławska ◽  
Popławski ◽  
Alseekh ◽  
Koblowska ◽  
Iwanicka-Nowicka ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Pentose Phosphate Pathway ◽  
Cancer Metabolism ◽  
Target Genes ◽  
Tricarboxylic Acid Cycle ◽  
Cell Cancer ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Gas Chromatography Mass Spectrometry ◽  
Arginine Metabolism

Metabolic reprogramming is one of the hallmarks of renal cell cancer (RCC). We hypothesized that altered metabolism of RCC cells results from dysregulation of microRNAs targeting metabolically relevant genes. Combined large-scale transcriptomic and metabolic analysis of RCC patients tissue samples revealed a group of microRNAs that contribute to metabolic reprogramming in RCC. miRNAs expressions correlated with their predicted target genes and with gas chromatography-mass spectrometry (GC-MS) metabolome profiles of RCC tumors. Assays performed in RCC-derived cell lines showed that miR-146a-5p and miR-155-5p targeted genes of PPP (the pentose phosphate pathway) (G6PD and TKT), the TCA (tricarboxylic acid cycle) cycle (SUCLG2), and arginine metabolism (GATM), respectively. miR-106b-5p and miR-122-5p regulated the NFAT5 osmoregulatory transcription factor. Altered expressions of G6PD, TKT, SUCLG2, GATM, miR-106b-5p, miR-155-5p, and miR-342-3p correlated with poor survival of RCC patients. miR-106b-5p, miR-146a-5p, and miR-342-3p stimulated proliferation of RCC cells. The analysis involving >6000 patients revealed that miR-34a-5p, miR-106b-5p, miR-146a-5p, and miR-155-5p are PanCancer metabomiRs possibly involved in global regulation of cancer metabolism. In conclusion, we found that microRNAs upregulated in renal cancer contribute to disturbed expression of key genes involved in the regulation of RCC metabolome. miR-146a-5p and miR-155-5p emerge as a key “metabomiRs” that target genes of crucial metabolic pathways (PPP (the pentose phosphate pathway), TCA cycle, and arginine metabolism).

scholarly journals A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo

2000 ◽  
Vol 192 (3) ◽  
pp. 359-366 ◽  
Author(s):  
Philip R. Taylor ◽  
Anna Carugati ◽  
Valerie A. Fadok ◽  
H. Terence Cook ◽  
Mark Andrews ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Apoptotic Cell ◽  
Classical Pathway ◽  
Apoptotic Cells ◽  
In Vivo Models ◽  
Complement Proteins ◽  
Apoptotic Cell Clearance ◽  
Cell Clearance ◽  
C1q Deficiency

The strongest susceptibility genes for the development of systemic lupus erythematosus (SLE) in humans are null mutants of classical pathway complement proteins. There is a hierarchy of disease susceptibility and severity according to the position of the missing protein in the activation pathway, with the severest disease associated with C1q deficiency. Here we demonstrate, using novel in vivo models of apoptotic cell clearance during sterile peritonitis, a similar hierarchical role for classical pathway complement proteins in vivo in the clearance of apoptotic cells by macrophages. Our results constitute the first demonstration of an impairment in the phagocytosis of apoptotic cells by macrophages in vivo in a mammalian system. Apoptotic cells are thought to be a major source of the autoantigens of SLE, and impairment of their removal by complement may explain the link between hereditary complement deficiency and the development of SLE.

scholarly journals Apoptotic cell clearance in systemic lupus erythematosus: I. Opsonization by antiphospholipid antibodies

1998 ◽  
Vol 41 (2) ◽  
pp. 205-214 ◽  
Author(s):  
Angelo A. Manfredi ◽  
Patrizia Rovere ◽  
Giacomo Galati ◽  
Silvia Heltai ◽  
Enrica Bozzolo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Apoptotic Cell ◽  
Systemic Lupus ◽  
Apoptotic Cell Clearance ◽  
Cell Clearance

scholarly journals Cellular metabolic reprogramming controls sugar appetite

2019 ◽  
Author(s):  
Zita Carvalho-Santos ◽  
Rita Cardoso Figueiredo ◽  
Ana Paula Elias ◽  
Carlos Ribeiro
Keyword(s):  
Cell Growth ◽  
Metabolic Pathway ◽  
Pentose Phosphate Pathway ◽  
Fat Body ◽  
Pentose Phosphate ◽  
Cellular Reprogramming ◽  
Metabolic Reprogramming ◽  
Animal Physiology ◽  
Small Set ◽  
Female Germline

Cellular metabolic reprogramming is an important mechanism by which cells rewire their metabolism to promote proliferation and cell growth. This process has been mostly studied in the context of tumorigenesis and less is known about its relevance for non-pathological processes and how it affects whole animal physiology. Here, we show that Drosophila female germline cells reprogram their carbohydrate metabolism, upregulating the pentose phosphate pathway (PPP) to produce eggs. Strikingly, this cellular reprogramming strongly impacts nutrient preferences. PPP activity in the germline specifically increases the animal’s appetite for sugar, the key nutrient fueling this metabolic pathway. We furthermore provide functional evidence that the germline alters sugar appetite by regulating the expression of the fat body secreted satiety factor fit. The cellular metabolic program of a small set of cells is therefore able to increase the animal’s preference for specific nutrients through inter-organ communication to promote specific metabolic and cellular outcomes.

scholarly journals Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1674
Author(s):  
Bo-Min Kim ◽  
Ye-Ji Lee ◽  
Youn-Hee Choi ◽  
Eun-Mi Park ◽  
Jihee Lee Kang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Apoptotic Cell ◽  
Alveolar Epithelial Cell ◽  
Lung Edema ◽  
Mouse Bone Marrow ◽  
Apoptotic Cell Clearance ◽  
Cell Clearance ◽  
Apoptotic Effects

Acute lung injury (ALI) is characterized by alveolar damage, lung edema, and exacerbated inflammatory response. Growth arrest-specific protein 6 (Gas6) mediates many different functions, including cell survival, proliferation, inflammatory signaling, and apoptotic cell clearance (efferocytosis). The role of Gas6 in bleomycin (BLM)-induced ALI is unknown. We investigated whether exogenous administration of mouse recombinant Gas6 (rGas6) has anti-inflammatory and anti-apoptotic effects on BLM-induced ALI. Compared to mice treated with only BLM, the administration of rGas6 reduced the secretion of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2, and increased the secretion of hepatocyte growth factor in bronchoalveolar lavage (BAL) fluid. rGas6 administration also reduced BLM-induced inflammation and apoptosis as evidenced by reduced neutrophil recruitment into the lungs, total protein levels in BAL fluid, caspase-3 activity, and TUNEL-positive lung cells in lung tissue. Apoptotic cell clearance by alveolar macrophages was also enhanced in mice treated with both BLM and rGas6 compared with mice treated with only BLM. rGas6 also had pro-resolving and anti-apoptotic effects in mouse bone marrow-derived macrophages and alveolar epithelial cell lines stimulated with BLM in vitro. These findings indicate that rGas6 may play a protective role in BLM-induced ALI.

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