Interaction of palmitate and LPS regulates cytokine expression and apoptosis through sphingolipids in human retinal microvascular endothelial cells

Lu, Zhongyang; Li, Yanchun; Ru, Ji Hyun; Lopes‐Virella, Maria F.; Lyons, Timothy J.; Huang, Yan

doi:10.1016/j.exer.2018.09.016

Cited by 13 publications

(14 citation statements)

References 49 publications

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“…OxLDL potentiates microvascular injury [ 219 ]. In human retinal microvascular endothelial cells, palmitate interacts with lipopolysaccharide, both of which are increased in T2DM, to upregulate IL-6 expression via CD36 [ 18 ].…”

Section: The Role Of Cd36 In Diabetic Complicationsmentioning

confidence: 99%

“…Conditions such as hyperglycemia and dyslipidemia significantly change CD36 expression, its function, and its signaling pathways. The CD36-dependent mechanisms are important events in the pathogenesis of diabetic complications, such as nephropathy [ 14 , 15 , 16 , 17 ], retinopathy [ 18 , 19 , 20 ], neuropathy [ 21 , 22 ], and cardiomyopathy [ 23 , 24 , 25 , 26 ]. Importantly, CD36 disrupts the functions of organs in a tissue-specific manner by several different mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, CD36 disrupts the functions of organs in a tissue-specific manner by several different mechanisms. The abnormalities of carbohydrate and lipid metabolism correlate with changes to CD36 expression and subcellular localization [ 8 , 10 , 14 , 15 , 16 , 25 , 27 , 28 , 29 , 30 , 31 , 32 ] and contribute to an increase in uptake of fatty acids (FAs) and modified lipoproteins; intracellular accumulation of lipids such as triacylglycerols (TAGs), diacylglycerols (DAGs), and ceramides (CERs); and oxidative and endoplasmic reticulum (ER) stress—and thus activation of a number of signaling pathways that initiate inflammation, modulate insulin response and the utilization of energy substrates, and stimulate cell death and fibrosis leading to progressive, often irreversible organ dysfunction [ 5 , 7 , 9 , 10 , 11 , 14 , 15 , 16 , 18 , 19 , 22 , 23 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring

Puchałowicz

Rać

2020

Cells

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CD36 is a multiligand receptor contributing to glucose and lipid metabolism, immune response, inflammation, thrombosis, and fibrosis. A wide range of tissue expression includes cells sensitive to metabolic abnormalities associated with metabolic syndrome and diabetes mellitus (DM), such as monocytes and macrophages, epithelial cells, adipocytes, hepatocytes, skeletal and cardiac myocytes, pancreatic β-cells, kidney glomeruli and tubules cells, pericytes and pigment epithelium cells of the retina, and Schwann cells. These features make CD36 an important component of the pathogenesis of DM and its complications, but also a promising target in the treatment of these disorders. The detrimental effects of CD36 signaling are mediated by the uptake of fatty acids and modified lipoproteins, deposition of lipids and their lipotoxicity, alterations in insulin response and the utilization of energy substrates, oxidative stress, inflammation, apoptosis, and fibrosis leading to the progressive, often irreversible organ dysfunction. This review summarizes the extensive knowledge of the contribution of CD36 to DM and its complications, including nephropathy, retinopathy, peripheral neuropathy, and cardiomyopathy.

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Section: The Role Of Cd36 In Diabetic Complicationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring

Puchałowicz

Rać

2020

Cells

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“…Many studies have shown that LPS induces intestinal inflammation, destroys intestinal structure and causes the release of inflammatory factors such as IL-6, IL-8, IL-1β, TNF-α and COX-2 [2][3][4][5]. Moreover, LPS activates the innate immune system and induces apoptosis [6]. A recent study shows that LPS promotes cell apoptosis through p38 and JNK pathways [7].…”

Section: Introductionmentioning

confidence: 99%

Ethyl pyruvate inhibits LPS induced IPEC-J2 inflammation and apoptosis through p38 and ERK1/2 pathways

Dong

Xue

et al. 2019

Cell Cycle

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The endotoxin of Gram-negative bacteria threatens the intestinal health of livestock. Ethyl pyruvate (EP) has been shown to regulate intestinal immunity and protect against cell and tissue damage. In this study, it was first verified that EP could reduce the secretion of IL-8, TNF-α, IL-6 and IL-1β in LPS-induced IPEC-J2 cells. Then, we used RNA sequencing (RNA-seq) to analyze the differentially expressed genes (DEGs) of inflammatory factors induced by LPS in IPEC-J2 cells. It was found that LPS induced the upregulation of 377 genes and the downregulation of 477 genes compared to Vehicle; LPS+EP induced the upregulation of 258 genes and the downregulation of 240 genes compared to Vehicle; and LPS+EP induced the upregulation of 373 genes and the downregulation of 188 genes compared to LPS (fold change > 1.5 and FDR < 0.01). Their enrichment pathways included the MAPK signaling pathway, PI3K-Akt signaling pathway, Tolllike receptor signaling pathway, and other pathways. Furthermore, the mRNA level of cytokines associated with inflammation and apoptosis enriched in the MAPK pathway was verified by qRT-PCR. Western blots and immunofluorescence revealed that EP significantly inhibited phosphorylated p38 and phosphorylated-ERK1/2 protein expression levels (P < 0.05). The apoptosis due to LPS reduced by EP was significantly inhibited, as shown by Annexin V-FITC/PI staining. According to the results, EP inhibited the expression of IL-8, TNF-α, IL-6 and IL-1β as well as apoptosis by inhibiting the phosphorylation of p38 and ERK1/2 in LPS-induced IPEC-J2 cells.

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“…Moreover, sphingolipid metabolism, a complex network composed of interconnected metabolites with ceramide as the central hub, which can cooperate with Bax and Bak to increase mitochondrial metabolic e ciency. The role of sphingolipid metabolism during apoptosis has been extensively explored [34,35]. As the hub in sphingolipid metabolism, the increased level of ceramide can respond to the pro-apoptotic signal, inducing the key factors in the apoptosis cascade.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Reveals the Effects of Copper on Mitochondria-mediated Apoptosis in Kidney of Chicken (Gallus Gallus)

Liao¹,

Yang²,

Bai³

et al. 2021

Preprint

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Background: Copper (Cu), a common feed additive in diets for animals, is effective in improving growth performance and feed efficiency. However, excessive intake of Cu can cause toxic effects. Kidney is the main target organ of Cu, but the relationship between Cu-induced nephrotoxicity and its metabolic process remains unclear.Results: For deeply investigating the nephrotoxicity induced by Cu, a total of 240 broiler chicks were fed with different contents of Cu (11, 110, 220, and 330 mg/kg Cu) for 49 d in this study (60 chicks per group). The results of TUNEL staining showed that Cu could induce apoptosis in kidney with increasing of TUNEL-positive cells. Additionally, a total of 62 differential metabolites were detected by liquid chromatography-mass spectrometry (LC-MS), and mainly enriched in the metabolic pathways including riboflavin metabolism, glutathione metabolism, sphingolipid metabolism, and glycerophospholipid metabolism, which were closely related to mitochondrial metabolism. Meanwhile, the decrease of mitochondrial membrane potential, impairment of mitochondrial respiratory function, and the increase of mitochondrial membrane permeability indicated that renal mitochondria were damaged by excess Cu. Furthermore, the increase of mRNA and protein levels of Drp1, Bax, Bak-1, CytC, Caspase-3/cleaved Caspase-3 and the decrease of mRNA and protein levels of OPA1, Mfn1, Mfn2, and Bcl-2 confirmed that Cu could induce mitochondria-mediated apoptosis in kidney.Conclusions: These results highlighted that mitochondrial metabolism could be considered as an important factor in influencing Cu toxicity, which for further demonstrating that Cu could induce mitochondria-mediated apoptosis in kidney of broilers.

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Interaction of palmitate and LPS regulates cytokine expression and apoptosis through sphingolipids in human retinal microvascular endothelial cells

Cited by 13 publications

References 49 publications

The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring

The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring

Ethyl pyruvate inhibits LPS induced IPEC-J2 inflammation and apoptosis through p38 and ERK1/2 pathways

Metabolomics Reveals the Effects of Copper on Mitochondria-mediated Apoptosis in Kidney of Chicken (Gallus Gallus)

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