scholarly journals Inhibitory effect of black raspberry extract on AGE accumulation and degradation, and ROS production in HUVEC cells

2020 ◽  
Vol 10 (6) ◽  
pp. 242
Author(s):  
Katsuaki Dan ◽  
Atsushi Takada ◽  
Yasunori Kanaho ◽  
Yuko Kusumi ◽  
Harutaka Banno
Keyword(s):  
Protein Expression ◽  
Inhibitory Effect ◽  
Expression Level ◽  
Mrna Levels ◽  
Ros Production ◽  
Black Raspberry ◽  
Cellular Events ◽  
Age Related ◽  
Berry Extracts ◽  
Age Receptors

Background: A critical event in age-related diseases involves the glycation of various proteins in the animal body to generate advanced glycation end products (AGEs). We have previously found that black raspberry extract (BRE) has effects on age-related diseases. From this observation, we expected that berry extracts, specifically BRE, would have positive effects on AGE-stimulated cell events that link to age-related diseases.Objective: To discuss the potency of berry extracts against diseases attributable to the AGE-dependent changes of cellular events, in this study, we examined the effects of berry extracts on the cellular events changed upon AGE stimulation of human umbilical vein endothelial cells (HUVECs) through AGE receptors.Methods: After HUVECs were incubated with AGE-BSA in the presence of serially diluted berry extracts, mRNA and protein levels of AGE receptors, intracellular AGE accumulation, and ROS production in the cell were determined by qRT-PCR and Western blotting, ELISA, and staining with the fluorescent probe, respectively.Results: Although concentration-dependent effects of berry extracts tested on mRNA levels of AGE receptors in HUVECs were not clear, mRNA level of the AGE receptor RAGE that is involved in the intracellular ROS production was increased by Blabina, which contains BRE, and the well-known anti-glycation compound aminoguanidine (AGD). In contrast, the protein expression level of RAGE was decreased by BRE and Blabina, but not by AGD. It was also found that BRE and Blabina suppressed AGE-BSA-stimulated ROS production in HUVECs. The extent of inhibition in the RAGE protein expression by BRE and Blabina was correlated well with the ROS generation measured in these samples.Conclusions: The results obtained in this study demonstrate that BRE has the most potent inhibitory effect on ROS accumulation in the cell, probably due to the suppression in the expression level of the RAGE protein. These observations suggest that black raspberry could be a potential nutraceutical to prevent various age-related diseases.Keywords: AGEs; RAGE; ROS; black raspberry; HUVECs. 

scholarly journals Aldosterone up-regulates voltage-gated potassium currents and NKCC1 protein membrane fractions

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Parveen Bazard ◽  
Bo Ding ◽  
Harish K. Chittam ◽  
Xiaoxia Zhu ◽  
Thomas A. Parks ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mineralocorticoid Receptor ◽  
Therapeutic Potential ◽  
Potassium Currents ◽  
Chloride Ions ◽  
Mrna Levels ◽  
Mineralocorticoid Receptor Antagonist ◽  
Voltage Gated ◽  
Age Related

Abstract Na+–K+–2Cl− Cotransporter (NKCC1) is a protein that aids in the active transport of sodium, potassium, and chloride ions across cell membranes. It has been shown that long-term systemic treatment with aldosterone (ALD) can enhance NKCC1 protein expression and activity in the aging cochlea resulting in improved hearing. In the present work, we used a cell line with confirmed NKCC1 expression to demonstrate that in vitro application of ALD increased outward voltage-gated potassium currents significantly, and simultaneously upregulated whole lysate and membrane portion NKCC1 protein expression. These ALD-induced changes were blocked by applying the mineralocorticoid receptor antagonist eplerenone. However, application of the NKCC1 inhibitor bumetanide or the potassium channel antagonist Tetraethyl ammonium had no effect. In addition, NKKC1 mRNA levels remained stable, indicating that ALD modulates NKCC1 protein expression via the activation of mineralocorticoid receptors and post-transcriptional modifications. Further, in vitro electrophysiology experiments, with ALD in the presence of NKCC1, K+ channel and mineralocorticoid receptor inhibitors, revealed interactions between NKCC1 and outward K+ channels, mediated by a mineralocorticoid receptor-ALD complex. These results provide evidence of the therapeutic potential of ALD for the prevention/treatment of inner ear disorders such as age-related hearing loss.

scholarly journals Icariin Intervenes in Cardiac Inflammaging through Upregulation of SIRT6 Enzyme Activity and Inhibition of the NF-Kappa B Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Yang Chen ◽  
Tao Sun ◽  
Junzhen Wu ◽  
Bill Kalionis ◽  
Changcheng Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Enzymatic Activity ◽  
Histone Deacetylase ◽  
Target Genes ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Cell Models ◽  
Animal Tissues ◽  
Nf Kappa B ◽  
Downstream Target

The aim of the study was to investigate the effect of icariin (ICA) on cardiac aging through its effects on the SIRT6 enzyme and on the NF-κB pathway. Investigating the effect of ICA on the enzymatic activity of histone deacetylase SIRT6 revealed a concentration of 10−8 mol/L ICA had a maximum activating effect on histone deacetylase SIRT6 enzymatic activity. Western analysis showed that ICA upregulated SIRT6 protein expression and downregulated NF-κB (p65) protein expression in animal tissues and cell models. ICA upregulated the expression of SIRT6 and had an inhibitory effect on NF-κB inflammatory signaling pathways as shown by decreasing mRNA levels of the NF-κB downstream target genes TNF-α, ICAM-1, IL-2, and IL-6. Those effects were mediated directly or indirectly by SIRT6. We provided evidence that inflammaging may involve a novel link between the effects of ICA on SIRT6 (a regulator of aging) and NF-κB (a regulator of inflammation).

scholarly journals Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2346
Author(s):  
Aline Yammine ◽  
Amira Zarrouk ◽  
Thomas Nury ◽  
Anne Vejux ◽  
Norbert Latruffe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Expression Level ◽  
Cholesterol Oxidation ◽  
Mrna Levels ◽  
Antioxidant Genes ◽  
Dietary Polyphenols ◽  
N2a Cells ◽  
Age Related ◽  
The Impact

The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death. When associated with RSV, QCT and API (3.125; 6.25 µM), 7KC-induced toxicity was reduced. The ability of QCT, RSV and API to prevent 7KC-induced oxidative stress was characterized by a decrease in reactive oxygen species (ROS) production in whole cells and at the mitochondrial level; by an attenuation of the increase in the level and activity of catalase; by attenuating the decrease in the expression, level and activity of glutathione peroxidase 1 (GPx1); by normalizing the expression, level and activity of superoxide dismutases 1 and 2 (SOD1, SOD2); and by reducing the decrease in the expression of nuclear erythroid 2-like factor 2 (Nrf2) which regulates antioxidant genes. QCT, RSV and API also prevented mitochondrial dysfunction in 7KC-treated cells by counteracting the loss of mitochondrial membrane potential (ΨΔm) and attenuating the decreased gene expression and/or protein level of AMP-activated protein kinase α (AMPKα), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) implicated in mitochondrial biogenesis. At the peroxisomal level, QCT, RSV and API prevented the impact of 7KC by counteracting the decrease in ATP binding cassette subfamily D member (ABCD)3 (a peroxisomal mass marker) at the protein and mRNA levels, as well as the decreased expresssion of genes associated with peroxisomal biogenesis (Pex13, Pex14) and peroxisomal β-oxidation (Abcd1, Acox1, Mfp2, Thiolase A). The 7KC-induced decrease in ABCD1 and multifunctional enzyme type 2 (MFP2), two proteins involved in peroxisomal β-oxidation, was also attenuated by RSV, QCT and API. 7KC-induced cell death, which has characteristics of apoptosis (cells with fragmented and/or condensed nuclei; cleaved caspase-3; Poly(ADP-ribose) polymerase (PARP) fragmentation) and autophagy (cells with monodansyl cadaverine positive vacuoles; activation of microtubule associated protein 1 light chain 3–I (LC3-I) to LC3-II, was also strongly attenuated by RSV, QCT and API. Thus, in N2a cells, 7KC induces a mode of cell death by oxiapoptophagy, including criteria of OXIdative stress, APOPTOsis and autoPHAGY, associated with mitochondrial and peroxisomal dysfunction, which is counteracted by RSV, QCT, and API reinforcing the interest for these polyphenols in prevention of diseases associated with increased 7KC levels.

scholarly journals Age-Related Changes in Sirtuin 7 Expression in Calorie-Restricted and Refed Rats

Gerontology ◽  
2015 ◽  
Vol 62 (3) ◽  
pp. 304-310 ◽  
Author(s):  
Agata Wronska ◽  
Aleksandra Lawniczak ◽  
Piotr M. Wierzbicki ◽  
Zbigniew Kmiec
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Calorie Restriction ◽  
Ribosome Biogenesis ◽  
Healthy Aging ◽  
Mrna Levels ◽  
Age Related ◽  
Mrna And Protein Expression ◽  
Old Rats ◽  
Age Related Changes

Background: Sirtuins (SIRT1-7) have been implicated to mediate the beneficial effects of calorie restriction for healthy aging. While the physiological functions of SIRT7 are still poorly understood, SIRT7 has recently been shown to affect ribosome biogenesis, mitochondrial gene expression, and hepatic lipid metabolism. Objective: To analyze the effects of age and short-term calorie restriction (SCR) and subsequent refeeding on SIRT7 expression in key metabolic tissues. Methods: Four- and 24-month-old male Wistar rats were subjected to 40% SCR for 30 days, followed by ad libitum feeding for 2 or 4 days. Liver, white adipose tissue (WAT), heart and skeletal muscle samples were analyzed by real-time PCR and Western blotting for SIRT7 mRNA and protein expression, respectively. Results: Aging had diverse effects on SIRT7 levels in lipogenic tissues: both the mRNA and protein levels increased in the retroperitoneal depot (rWAT), did not change in the epididymal depot (eWAT), and decreased in the subcutaneous depot (sWAT) and the liver of old as compared to young animals. In the heart, extensor digitorum longus muscle (EDL) and soleus muscle (SOL), Sirt7 gene but not protein expression was lower in old than in young control rats. SCR did not affect SIRT7 expression in WAT and the liver in both age groups. In the heart of young animals, SCR did not affect SIRT7 mRNA or protein level. In EDL, SIRT7 protein but not mRNA levels decreased after SCR and remained reduced upon refeeding. In SOL, both SIRT7 mRNA and protein expression were inhibited by refeeding. In old rats, cardiac Sirt7 expression increased after SCR and refeeding. In old rats' EDL and SOL muscles, SIRT7 protein expression was inhibited by refeeding. Conclusion: Age-related changes of SIRT7 gene expression in key organs of energy homeostasis are tissue dependent.

scholarly journals Phosphorylation at Serines 157 and 161 Is Necessary for Preserving Cardiac Expression Level and Functions of Sarcomeric Z-Disc Protein Telethonin

2021 ◽  
Vol 12 ◽  
Author(s):  
Hannah R. Lewis ◽  
Seda Eminaga ◽  
Mathias Gautel ◽  
Metin Avkiran
Keyword(s):  
Protein Expression ◽  
Gene Dosage ◽  
Systolic Dysfunction ◽  
Ubiquitin Proteasome System ◽  
Expression Level ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Adrenergic Stimulation ◽  
Protein Expression Level

Aims: In cardiac myocytes, the sarcomeric Z-disc protein telethonin is constitutively bis-phosphorylated at C-terminal residues S157 and S161; however, the functional significance of this phosphorylation is not known. We sought to assess the significance of telethonin phosphorylation in vivo, using a novel knock-in (KI) mouse model generated to express non-phosphorylatable telethonin (TcapS157/161A).Methods and Results:TcapS157/161A and wild-type (WT) littermates were characterized by echocardiography at baseline and after sustained β-adrenergic stimulation via isoprenaline infusion. Heart tissues were collected for gravimetric, biochemical, and histological analyses. At baseline, TcapS157/161A mice did not show any variances in cardiac structure or function compared with WT littermates and mutant telethonin remained localized to the Z-disc. Ablation of telethonin phosphorylation sites resulted in a gene-dosage dependent decrease in the cardiac telethonin protein expression level in mice carrying the S157/161A alleles, without any alteration in telethonin mRNA levels. The proteasome inhibitor MG132 significantly increased the expression level of S157/161A telethonin protein in myocytes from TcapS157/161A mice, but not telethonin protein in myocytes from WT mice, indicating a role for the ubiquitin–proteasome system in the regulation of telethonin protein expression level. TcapS157/161A mice challenged with sustained β-adrenergic stimulation via isoprenaline infusion developed cardiac hypertrophy accompanied by mild systolic dysfunction. Furthermore, the telethonin protein expression level was significantly increased in WT mice following isoprenaline stimulation but this response was blunted in TcapS157/161A mice.Conclusion: Overall, these data reveal that telethonin protein turnover in vivo is regulated in a novel phosphorylation-dependent manner and suggest that C-terminal phosphorylation may protect telethonin against proteasomal degradation and preserve cardiac function during hemodynamic stress. Given that human telethonin C-terminal mutations have been associated with cardiac and skeletal myopathies, further research on their potential impact on phosphorylation-dependent regulation of telethonin protein expression could provide valuable mechanistic insight into those myopathies.

scholarly journals 3β,23-Dihydroxy-12-ene-28-ursolic Acid Isolated from Cyclocarya paliurus Alleviates NLRP3 Inflammasome-Mediated Gout via PI3K-AKT-mTOR-Dependent Autophagy

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Dongxiao Lou ◽  
Xiaogai Zhang ◽  
Cuihua Jiang ◽  
Fang Zhang ◽  
Chao Xu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Ursolic Acid ◽  
Nlrp3 Inflammasome ◽  
Soft Tissues ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Expression Level ◽  
Expression Ratio ◽  
Cyclocarya Paliurus ◽  
Caspase 1

Gout is regarded as a painful inflammatory arthritis induced by the deposition of monosodium urate crystals in joints and soft tissues. Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated IL-1β production plays a crucial role in the pathological process of gout. Cyclocarya paliurus (CP) tea was found to have an effect on reducing the blood uric acid level of people with hyperuricemia and gout. However, its medicinal ingredients and mechanism for the treatment of gout are still unclear. Thus, this study was designed to investigate the effects of the active triterpenoids isolated from C. paliurus on gout and explore the underlying mechanism. The results showed that compound 2 (3β,23-dihydroxy-12-ene-28-ursolic acid) from C. paliurus significantly decreased the protein expression of IL-1β, caspase-1, pro-IL-1β, pro-caspase-1, and NLRP3. Furthermore, the production of ROS in the intracellular was reduced after compound 2 treatment. However, ROS agonist rotenone remarkably reversed the inhibitory effect of compound 2 on the protein expression of NLRP3 inflammasome. Additionally, the expression level of LC3 and the ratio of LC3II/LC3I were increased, but the expression level of p62 was suppressed by compound 2 whereas an autophagy inhibitor 3-methyladenine (3-MA) significantly abolished the inhibitory effects of compound 2 on the generation of ROS and the protein expression of NLRP3 inflammasome. Moreover, compound 2 could ameliorate the expression ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Interestingly, mTOR activator MHY-1485 could block the promotion effect of compound 2 on autophagy regulation and inhibitory effect of compound 2 on induction of ROS and IL-1β. In conclusion, these findings suggested that compound 2 may effectively improve NLRP3 inflammasome-mediated gout via PI3K-AKT-mTOR-dependent autophagy and could be further investigated as a potential agent against gout.

Increased Superoxide Levels, HO-1 and Fyn Protein Expression in Bcr/abl Overexpressing Cells: Implications for Adaptation and Survival in an Oxidatively Challenging Environment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4403-4403
Author(s):  
Joya Chandra ◽  
Kechen Ban
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Disease Progression ◽  
Mapk Pathway ◽  
Antioxidant Properties ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Ros Production ◽  
Challenging Environment

Abstract The bcr/abl oncogene is present in the majority of CML and in a subset of ALL patients. In addition to anti-apoptotic properties, proliferative advantages and growth factor independence, the presence of the Bcr/abl kinase raises intracellular levels of reactive oxygen species (ROS). Increased ROS in CML have been linked to DNA damage and DNA repair deficiencies with implications for promoting genomic instability and secondary mutations associated with disease progression. Here we show that superoxide is the specific ROS entity that is elevated when Bcr/abl is overexpressed in an IL-3 dependent pre-B cell line, BaF3. Strikingly, treatment with classical oxidants, such as hydrogen peroxide or tert-butyl peroxide, demonstrated an inherent resistance to oxidative stress induced apoptosis in Bcr/abl-containing cells, suggesting that antioxidant defenses activated by Bcr/abl as a response to the increased endogenous ROS production may promote survival in Bcr/abl positive populations. In an effort to characterize the redox environment in Bcr/abl containing cells, we examined several antioxidant enzymes that are known downstream substrates of c-abl or bcr/abl, including peroxiredoxin, catalase and heme oxygenase-1 (HO-1). Of these, HO-1 protein expression was three fold higher in Bcr/abl transductants, consistent with a reported role for HO-1 as a Bcr/abl dependent survival factor. Interestingly, the Src family kinase, Fyn, which can be activated by oxidative stress, was increased four fold in Bcr/abl overexpressing cells. This is consistent with reported microarray data in which fyn mRNA levels are higher in Philadelphia positive leukemias than non-Philapdelphia positive leukemias. Other components of ROS responsive signaling pathways were also interrogated including the Mapk pathway and Akt pathway, with no difference noted between parental and Bcr/abl overexpressing cells. Our data suggest a relationship between Bcr/abl-induced superoxide elevation, resistance to oxidative stress, elevation of HO-1 (which has antioxidant properties) and elevated Fyn (a putative downstream target for ROS production). These redox alterations and their consequences may equip Bcr/abl positive cells with a survival and/or proliferative advantage in an oxidatively challenging environment, thus promoting disease progression and blast crisis.

Abstract P212: Peroxiredoxin-4 And Dopamine D5 Receptor Interact To Reduce Oxidative Stress And Inflammation In The Kidney

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Hewang Lee ◽  
Sufei Yang ◽  
Peiying Yu ◽  
Ines Armando ◽  
Chunyu Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Protein Expression ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Ros Production ◽  
Hek 293 ◽  
Amplex Red ◽  
Renal Proximal Tubule Cells ◽  
Dopamine D5 Receptor

Peroxiredoxin-4 (PRDX4), an endoplasmic reticulum peroxiredoxin protein, plays a protective role against oxidative stress and inflammation by reducing hydrogen peroxide to water. The dopamine D5 receptor (D 5 R) is also important in protecting against oxidative stress, but the interaction between PRDX4 and D 5 R in regulating oxidative stress in the kidney is not known. In D 5 R-HEK 293 cells, fenoldopam (FEN, 25 nM/12 hr, n=4), a D1-likereceptor agonist, increased PRDX4 protein expression (1.92±0.12-fold over basal level, n=4), mainly in non-lipid rafts (LRs: 24.9±11.4%, non-LRs: 75.1±11.4%, baseline; LRs: 30.9±13.9%, non-LRs: 174.1±16.7%, FEN). FEN also increased the co-immunoprecipitation of D 5 R and PRDX4 and their colocalization, particularly in the endoplasmic reticulum. In human renal proximal tubule cells (hRPTCs), FEN (25 nM/12 hr, n=3) increased PRDX4 and D 5 R interaction in non-LRs, also. Si-RNA silencing of PRDX4 increased reactive oxygen species (ROS) production and impaired the inhibitory effect of FEN on ROS production (scrambled siRNA: 100.0±11.6% and 65.4±5.6% for Vehicle (Veh) and FEN, respectively; PRDX4 siRNA: 147.7±11.8% and 134.8±11.2% for Veh and FEN, respectively, n=4/group) detected by Amplex Red. In addition in both D 5 R-HEK 293 and hRPTCs, siRNA silencing of PRDX4 increased the production of interleukin-1β (26.88±3.8 and 46.40±4.2 pg/mL [n=3, D 5 R-HEK 293]; 15.87±1.2 and 37.9±1.4 pg/mL [n=3 in hRPTCs]), tumor necrosis factor (131.7±6.5 and 271.2±18.1 pg/mL [n=4, D 5 R-HEK 293]; 108.8±11.8 and 240.1±13.7 pg/mL [n=4 in hRPTCs]), and caspase-12 (15.21±3.8 and 40.78±4.3 ng/mL [n=4,n D 5 R-HEK 293]; 8.8±1.1 and 27.9±2.0 ng/mL [n=4, hRPTCs]). Furthermore, the protein expression of D 5 R was decreased in PRDX4 siRNA-treated D 5 R-HEK293 (~41.2%, n=3) and hRPTCs (~39.6%, n=3). PRDX4 protein was also reduced in the kidney homogenates from D 5 R -/- mice (WT: 1.00±0.18, n=5; D 5 R -/- : 0.686±0.14, n=4; P<0.05). Taken together, PRDX4 interacts with D 5 R to decrease oxidative stress and inflammation in the kidney.

scholarly journals β-Catenin Regulation in Sporadic Colorectal Carcinogenesis: Not as Simple as APC

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ernst Fredericks ◽  
Gill Dealtry ◽  
Saartjie Roux
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Statistical Significance ◽  
Inhibitory Effect ◽  
Colorectal Carcinogenesis ◽  
Sporadic Colorectal Cancer ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cox 2

Background. The wnt/APC/β-catenin pathway is a critical initiator in colorectal carcinogenesis in both hereditary and sporadic colorectal cancer (CRC). The progression of this process remains incompletely understood, although inflammation is pivotal. Drivers of inflammation are elevated in malignant tissue and have been shown to regulate β-catenin expression. Interleukin-17A (IL-17A) is protumorigenic at elevated levels via COX-2 stimulation. Elevated peroxisome proliferator-activated receptor γ (PPARγ) expression has reduced risk of carcinogenesis and good overall prognosis in established CRC. Activation of PPARγ has inhibitory effect on β-catenin. Methods. Using qPCR and IHC, we compared β-catenin, PPARγ, COX-2, and IL-17A in the colonic mucosa of patients with sporadic CRC, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS), against a normal control population. Results. β-catenin mRNA and protein expression progressively increased from the Normal group, through IBS and IBD reaching statistical significance in CRC. COX-2 mRNA levels increased similarly with statistical significance in IBD and CRC. However, COX-2 protein expression was inverted with significant expression in the Normal and IBS groups and reduced levels in IBD and CRC. PPARγ mRNA expression was unchanged in IBD and CRC but was significantly elevated in the IBS. IL-17A mRNA was significantly reduced in IBS and CRC but unchanged in IBD. There were no differences in all parameters tested in the Normal and IBS groups. Conclusion. β-catenin is confirmed as a major driver of colorectal carcinogenesis but is controlled by many more players other than APC. Elevated levels of PPARγ may have an anticarcinogenic effect. The role of COX-2 expression, especially its posttranscriptional regulation in colorectal cancer, needs further elucidation.

Curcumin Inhibits the Proteolytic Process of SREBP-2 by First Inhibiting the Expression of S1P rather than Directly Inhibiting SREBP-2 Expression.

2020 ◽  
Author(s):  
Yongnan Li ◽  
Shuodong Wu
Keyword(s):  
Transcription Factor ◽  
Protein Expression ◽  
Cholesterol Metabolism ◽  
Regulatory Element ◽  
Inhibitory Effect ◽  
Specific Protein ◽  
Mrna Levels ◽  
Curcumin Treatment ◽  
Short Period ◽  
Sterol Regulatory Element

Abstract Objective: Many studies have demonstrated that curcumin can downregulate mRNA levels of sterol regulatory element-binding proteins (SREBP-2), however, our study did not find similar results. This study was designed to demonstrate that curcumin inhibits the proteolytic process of SREBP-2 by first inhibiting the expression of membrane-bound transcription factor site-1 protease (S1P) rather than directly inhibiting SREBP-2 expression.Methods: After curcumin treatment, Caco-2 cells were collected to observe the dose- and time-dependent dynamics of precursor and mature SREBP-2, transcription factor specific protein 1 (SP-1) and SREBP cleavage-activating protein (SCAP). After curcumin treatment, SREBP-2 distribution was detected in the cells and S1P protein expression were examined.Results: Curcumin could downregulate mRNA levels of SREBP2, SP-1 and SCAP, but it did not simultaneously downregulate the expression of precursor SREBP-2 (pSREBP-2) and SCAP. Curcumin can inhibit the proteolytic process of SREBP-2, reduce the production of mature SREBP-2 (mSREBP-2) and change the cellular distribution of SREBP-2. The inhibitory effect of curcumin on SP-1 protein expression is short-acting. Conclusion: Curcumin can inhibit the SREBP-2 proteolytic process to reduce mSREBP-2 which functions as a transcription factor, affecting the regulation of cholesterol metabolism-related genes. This process may be achieved by regulating the expression of S1P. Curcumin does not directly inhibit the expression of mSREBP-2 protein, and it has no such inhibitory effect for at least a short period of time, although curcumin does reduce the amount of mSREBP-2 protein.

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