CCAAT/enhancer-binding protein beta (C/EBPβ) knockdown reduces inflammation, ER stress, and apoptosis, and promotes autophagy in oxLDL-treated RAW264.7 macrophage cells

Zahid, Muhammad; Rogowski, Michael; Ponce, Christopher; Choudhury, Mahua; Moustaid‐Moussa, Naima; Rahman, Shaikh Mizanoor

doi:10.1007/s11010-019-03642-4

Cited by 56 publications

(30 citation statements)

References 65 publications

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“…In addition to CLOCK, our gene enrichment analysis identified nine other transcriptions factors (TCF21, AR, SLAL4, SMAD2, SMAD3, OOAR, OCT4, CDX2, and CEBPB), which are implicated in various cellular processes, including metabolism [63,64], inflammation [65][66][67], rhythmic activation of circadian cycle repressors [68], and maintenance of the pluripotency of stem cells [69][70][71][72]. Many of these factors act as key mediators of canonical signaling pathways such as SMAD2 and SMAD3, involved in TGF-β signaling.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Very Low Dose Particle Radiation on Gene Expression in the Heart: Degenerative Disease Risks

Garikipati

Arakelyan

Blakely

et al. 2021

Cells

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Compared to low doses of gamma irradiation (γ-IR), high-charge-and-energy (HZE) particle IR may have different biological response thresholds in cardiac tissue at lower doses, and these effects may be IR type and dose dependent. Three- to four-month-old female CB6F1/Hsd mice were exposed once to one of four different doses of the following types of radiation: γ-IR 137Cs (40-160 cGy, 0.662 MeV), 14Si-IR (4-32 cGy, 260 MeV/n), or 22Ti-IR (3-26 cGy, 1 GeV/n). At 16 months post-exposure, animals were sacrificed and hearts were harvested and archived as part of the NASA Space Radiation Tissue Sharing Forum. These heart tissue samples were used in our study for RNA isolation and microarray hybridization. Functional annotation of twofold up/down differentially expressed genes (DEGs) and bioinformatics analyses revealed the following: (i) there were no clear lower IR thresholds for HZE- or γ-IR; (ii) there were 12 common DEGs across all 3 IR types; (iii) these 12 overlapping genes predicted various degrees of cardiovascular, pulmonary, and metabolic diseases, cancer, and aging; and (iv) these 12 genes revealed an exclusive non-linear DEG pattern in 14Si- and 22Ti-IR-exposed hearts, whereas two-thirds of γ-IR-exposed hearts revealed a linear pattern of DEGs. Thus, our study may provide experimental evidence of excess relative risk (ERR) quantification of low/very low doses of full-body space-type IR-associated degenerative disease development.

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Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Very Low Dose Particle Radiation on Gene Expression in the Heart: Degenerative Disease Risks

Garikipati

Arakelyan

Blakely

et al. 2021

Cells

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“…Traditionally referred to as the translational arm, the PERK/eIF2A/CHOP arm regulate lipogenesis by controlling the processing and maturation of SREBP-1 and 2, C/EBPα, C/EBPβ and PPAR γ (Peroxisome proliferator activated receptor-gamma) ( Lakshmanan et al, 2013 ). Increased levels of ATF4 and CHOP triggers the transcription of ATG genes (AuTophagy-related Genes), a pro-survival mechanism of the cell, to clear off misfolded proteins with the help of lysosomes ( B’Chir et al, 2013 ; Zahid et al, 2020 ). However, chronic levels of ATF4 and CHOP due to persistent ER stress can induce cell death mechanisms by the activation of GADD34, ERO1 and Caspases ( Rozpedek et al, 2016 ).…”

Section: Lipid and Sterol Homeostasismentioning

confidence: 99%

Pathological Crosstalk Between Oxidized LDL and ER Stress in Human Diseases: A Comprehensive Review

Varghese

Ali

2021

Front. Cell Dev. Biol.

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The oxidative modification of the major cholesterol carrying lipoprotein, oxLDL, is a biomarker as well as a pathological factor in cardiovascular diseases (CVD), type 2 diabetes mellitus (T2DM), obesity and other metabolic diseases. Perturbed cellular homeostasis due to physiological, pathological and pharmacological factors hinder the proper functioning of the endoplasmic reticulum (ER), which is the major hub for protein folding and processing, lipid biosynthesis and calcium storage, thereby leading to ER stress. The cellular response to ER stress is marked by a defensive mechanism called unfolded protein response (UPR), wherein the cell adapts strategies that favor survival. Under conditions of excessive ER stress, when the survival mechanisms fail to restore balance, UPR switches to apoptosis and eliminates the defective cells. ER stress is a major hallmark in metabolic syndromes such as diabetes, non-alcoholic fatty liver disease (NAFLD), neurological and cardiovascular diseases. Though the pathological link between oxLDL and ER stress in cardiovascular diseases is well-documented, its involvement in other diseases is still largely unexplored. This review provides a deep insight into the common mechanisms in the pathogenicity of diseases involving oxLDL and ER stress as key players. In addition, the potential therapeutic intervention of the targets implicated in the pathogenic processes are also explored.

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“…ER stress can induce autophagy by regulating PERK and IRE1-dependent pathways. It was found that knockdown of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPβ) may induce the expression of autophagy-related proteins LC3A/B-II and ATG5, and at the same time, reduce phosphorylation of mammalian target of rapamycin protein (mTOR) and its gene expression in macrophages exposed to oxLDL [ 64 ]. Being a key cellular regulator of metabolism and autophagy, mTOR is tightly involved in cholesterol handling by cells.…”

Section: The Role Of Er Stress In Apoptosismentioning

confidence: 99%

“…The activity and subcellular localization of this factor is regulated by mTOR. Inhibition of mTOR can increase the expression of proteins involved in cholesterol efflux from macrophages by TFEB translocation into the nucleus [ 64 ]. Known triggers of apoptosis and their action are presented in Table 2 .…”

Section: The Role Of Er Stress In Apoptosismentioning

confidence: 99%

Endoplasmic Reticulum Stress in Macrophages: The Vicious Circle of Lipid Accumulation and Pro-Inflammatory Response

et al. 2020

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The endoplasmic reticulum (ER) stress is an important event in the pathogenesis of different human disorders, including atherosclerosis. ER stress leads to disturbance of cellular homeostasis, apoptosis, and in the case of macrophages, to foam cell formation and pro-inflammatory cytokines production. In atherosclerosis, several cell types can be affected by ER stress, including endothelial cells, vascular smooth muscular cells, and macrophages. Modified low-density lipoproteins (LDL) and cytokines, in turn, can provoke ER stress through different processes. The signaling cascades involved in ER stress initiation are complex and linked to other cellular processes, such as lysosomal biogenesis and functioning, autophagy, mitochondrial homeostasis, and energy production. In this review, we discuss the underlying mechanisms of ER stress formation and the interplay of lipid accumulation and pro-inflammatory response. We will specifically focus on macrophages, which are the key players in maintaining chronic inflammatory milieu in atherosclerotic lesions, and also a major source of lipid-accumulating foam cells.

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CCAAT/enhancer-binding protein beta (C/EBPβ) knockdown reduces inflammation, ER stress, and apoptosis, and promotes autophagy in oxLDL-treated RAW264.7 macrophage cells

Cited by 56 publications

References 65 publications

Long-Term Effects of Very Low Dose Particle Radiation on Gene Expression in the Heart: Degenerative Disease Risks

Long-Term Effects of Very Low Dose Particle Radiation on Gene Expression in the Heart: Degenerative Disease Risks

Pathological Crosstalk Between Oxidized LDL and ER Stress in Human Diseases: A Comprehensive Review

Endoplasmic Reticulum Stress in Macrophages: The Vicious Circle of Lipid Accumulation and Pro-Inflammatory Response

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