scholarly journals Kuntai Capsule Inhibited Endometriosis via Inducing Apoptosis in a Rat Model

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ruihua Zhong ◽  
Aying Ma ◽  
Jianping Zhu ◽  
Guoting Li ◽  
Shuwu Xie ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Protein Expression ◽  
Rat Model ◽  
Expression Profiles ◽  
Serum Levels ◽  
Dependent Manner ◽  
Western Blot Assay ◽  
Eutopic Endometrium ◽  
Protein Levels ◽  
Ectopic Endometrium

We evaluated the effectiveness of Kuntai Capsule (KTC) for treating endometriosis using rat model and investigated its preliminary mechanism of action involved. SD rats were implanted with endometrial tissues and treated with KTC for three weeks. Then, laparotomy was performed to examine volume changes of the autografts. The serum levels of TNF-α, IL-6, COX-2, E2, and P4 were measured through ELISA. TUNEL was performed to analyze the apoptosis on ectopic endometrium. Protein levels of caspases 8, 9, and 3 and cytochrome c in the ectopic and eutopic endometrium were measured by western blotting. Results showed that KTC significantly decreased the volumes of ectopic endometrium. The level of TNF-αincreased and E2decreased in the KTC treatment groups. TUNEL and western blot assay showed that KTC could induce apoptosis of endometriotic tissues, accompanied with the increased protein expression of caspases 8 and 9, activated caspase-3, and cytochrome c in a dose-dependent manner. However, these protein expression profiles were not affected in eutopic endometrium. Our findings suggest that KTC could inhibit the growth of ectopic endometrial tissue through upregulating the level of TNF-αand its downstream signaling, including caspases and cytochrome c.

Identification of a β1 integrin isoform with restricted tissue expression in a teleost fish

2011 ◽  
Vol 23 (5) ◽  
pp. 654 ◽  
Author(s):  
Patricia Castillo-Briceño ◽  
Isabel Cabas ◽  
Marta Arizcun ◽  
Jose Meseguer ◽  
Victoriano Mulero ◽  
...  
Keyword(s):  
Teleost Fish ◽  
Sparus Aurata ◽  
Expression Profiles ◽  
Specific Inhibitor ◽  
Serum Levels ◽  
Tissue Expression ◽  
Gilthead Seabream ◽  
Β1 Integrin ◽  
Dependent Manner ◽  
Tissue Remodelling

The composition and organisation of extracellular matrix (ECM)-related molecules change during development. These components interact with different cell surface receptors to modulate the transduction of signals for cell growth, differentiation, migration, proliferation and apoptosis. Previous findings in the teleost fish gilthead seabream (Sparus aurata L., Teleostei), a marine protandrous hermaphrodite fish, showed that endocrine and immune stimuli are able to modulate the expression of ECM-related molecules, as well as specific correlations between them. In the present study, quantitative reverse transcription–polymerase chain reaction was used to examine the gene expression profile of β1 integrin isoform b (ITGB1b) and its possible role in reproductive physiology, especially in relation to spermatogenesis. Expression profiles were analysed in the context of the reproductive cycle (RC) and in relation with other ECM-related molecules, including matrix metalloproteinase (MMP)-2, MMP-9, MMP-13, tissue-specific inhibitor of metalloproteinase (TIMP)-2a, TIMP-2b, collagen (COL1A1) and ITGB1a. Expression of ITGB1b was found in the testis and brain and, to some extent, in endothelial cells. In contrast, ITGB1a was expressed ubiquitously. In the testis, the ITGB1b expression peaked during spermatogenesis, whereas the expression of the other ECM-related molecules is induced mainly during the post-spawning stage, both stages of marked tissue remodelling during the first and second RC in males. In addition, in fish exposed to the endocrine disruptor 17α-ethynyloestradiol (at 5 and 50 μg g–1 food during 7, 14 and 21 days), ITGB1b expression in the testis was inhibited in a dose- and time-dependent manner and was related to reduced serum levels of testosterone. Together, these results suggest a different functionality for the two ITGB1 isoforms in the gilthead seabream, where ITGB1b is more specifically involved in reproduction. This is the first report of an ITGB1 gene isoform whose expression is restricted to endocrine-related tissues in vertebrates.

scholarly journals Co-Treatments of Edible Curcumin from Turmeric Rhizomes and Chemotherapeutic Drugs on Cytotoxicity and FLT3 Protein Expression in Leukemic Stem Cells

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5785
Author(s):  
Fah Chueahongthong ◽  
Singkome Tima ◽  
Sawitree Chiampanichayakul ◽  
Cory Berkland ◽  
Songyot Anuchapreeda
Keyword(s):  
Stem Cells ◽  
Protein Expression ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Chemotherapeutic Drugs ◽  
Protein Levels ◽  
Leukemic Cell Lines

This study aims to enhance efficacy and reduce toxicity of the combination treatment of a drug and curcumin (Cur) on leukemic stem cell and leukemic cell lines, including KG-1a and KG-1 (FLT3+ LSCs), EoL-1 (FLT3+ LCs), and U937 (FLT3− LCs). The cytotoxicity of co-treatments of doxorubicin (Dox) or idarubicin (Ida) at concentrations of the IC10–IC80 values and each concentration of Cur at the IC20, IC30, IC40, and IC50 values (conditions 1, 2, 3, and 4) was determined by MTT assays. Dox–Cur increased cytotoxicity in leukemic cells. Dox–Cur co-treatment showed additive and synergistic effects in several conditions. The effect of this co-treatment on FLT3 expression in KG-1a, KG-1, and EoL-1 cells was examined by Western blotting. Dox–Cur decreased FLT3 protein levels and total cell numbers in all the cell lines in a dose-dependent manner. In summary, this study exhibits a novel report of Dox–Cur co-treatment in both enhancing cytotoxicity of Dox and inhibiting cell proliferation via FLT3 protein expression in leukemia stem cells and leukemic cells. This is the option of leukemia treatment with reducing side effects of chemotherapeutic drugs to leukemia patients.

BCL2 Induces Suppressor of Cytokine Signaling-3 (SOCS3) Expression in Murine B Cells Via Pathways Involving an HSP70/90 Complex and Activation of p44/42 Map Kinase.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2199-2199
Author(s):  
Aric Parnes ◽  
Julie Kim ◽  
Sofya Rodov ◽  
K. Gary J. Vanasse
Keyword(s):  
B Cells ◽  
Protein Expression ◽  
Map Kinase ◽  
Dependent Manner ◽  
Protein Database ◽  
Protein Levels ◽  
Western Analysis ◽  
Socs3 Expression ◽  
Bcl2 Protein ◽  
Socs3 Protein

Abstract Polyclonal CD19+ B cells isolated from Bcl2-overexpressing Eμ-Bcl2 transgenic mice (Eμ-Bcl2tg+) overexpress SOCS3 protein. We previously reported that enforced expression of Bcl2 in BaF3 pro-B cells induces SOCS3 protein via p44/42 MAP Kinase activation. We also found that SOCS3 protein overexpression is an independent poor prognostic factor in patients with Bcl2-positive follicular lymphomas. We hypothesized that Bcl2 mediates induction of SOCS3 indirectly via cellular intermediaries that may alter cell signaling and/or apoptotic pathways in B cells. In the current study, magnetic bead B cell negative selection was used to isolate polyclonal CD19+ B cells from 24 week old Eμ-Bcl2tg+ mice (n=6). Bcl2-interacting proteins were then isolated from Eμ-Bcl2tg+ B cells by immunoprecipitation using a polyclonal anti-Bcl2 antibody. Bcl2 protein complexes separated by SDS-PAGE revealed several bands, with the most prominent bands noted at 70kDa and 90kDa, respectively. These bands were analyzed by mass spectrometry (LC MS/MS) and protein database analysis identified them as Heat Shock Proteins (HSP) 70 and 90β. LC MS/MS results were verified by co-immunoprecipitation of both HSP70 and HSP90β with Bcl2 in Eμ-Bcl2tg+ B cells. Co-immunoprecipitation assays with SOCS3 and Bax revealed no interaction with this protein complex. 5 × 106 Eμ-Bcl2tg+ B cells from individual mice were then cultured in microtiter plates using Supplented Iscove’s Modified Dulbecco’s Medium (SIMDM) with 10% FBS and were treated over 12 hours with escalating doses of the HSP90 inhibitor 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG). Immunoprecipitation with Bcl2 revealed that 17-AAG blocked the interaction between Bcl2 and HSP90β in a dose-dependent manner. Furthermore, Western analysis of Eμ-Bcl2tg+ B cells treated with 17-AAG revealed a marked decrease in SOCS3 protein expression compared with untreated cells. In addition, Eμ-Bcl2tg+ B cells exposed to increasing concentrations of 17-AAG showed a concentration-dependent increase in activity of caspase 3 and increased cell death compared with untreated cells. Next, to determine whether Bcl2-mediated SOCS3 overexpression in B cells involves STAT3-dependent or -independent mechanisms, we measured phospho-STAT3 levels relative to STAT3 in Eμ-Bcl2tg+ B cells cultured in the presence of escalating doses of IL-6. When probed with phospho-STAT3 and STAT3 antisera, Eμ-Bcl2tg+ B cells did not reveal STAT3 protein phosphorylation but revealed equivalent STAT3 protein levels in response to IL-6. Eμ-Bcl2tg+ B cells were then cultured as above in the presence or absence of a specific p44/42MAPK pathway inhibitor (MEK 1/2 inhibitor U0126), and whole cell lysates were analyzed for SOCS3 expression by Western analysis. When probed with SOCS3 antisera, B cells selectively grown in the presence of U0126 revealed complete abrogation of SOCS3 protein expression while those grown in the absence of inhibitor continued to harbor SOCS3 protein. Bcl2 protein levels remained unchanged in the presence or absence of U0126. Inhibitors of p38MAPK (SB203580), AKT (Triciribine), and PI3K (LY294002) did not affect SOCS3 expression. These results indicate that Bcl2-associated SOCS3 induction in murine B cells is dependent upon a HSP70/90 complex and involves activation of p44/42 MAPK. These studies illustrate a novel signaling pathway in B cells important for the regulation of caspase-mediated apoptosis.

scholarly journals Upregulation of UCP2 Expression Protects against LPS-Induced Oxidative Stress and Apoptosis in Cardiomyocytes

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jinda Huang ◽  
Wanwan Peng ◽  
Yijun Zheng ◽  
Hu Hao ◽  
Sitao Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Protein Level ◽  
Caspase 3 ◽  
Uncoupling Protein ◽  
Dependent Manner ◽  
Mitochondrial Cytochrome ◽  
Protein Levels ◽  
Ucp2 Expression ◽  
Mitochondrial Cytochrome C

Uncoupling protein 2 (UCP2) has a cardioprotective role under septic conditions, but the underlying mechanism remains unclear. This study aimed at investigating the effects of UCP2 on the oxidative stress and apoptosis of cardiomyocytes induced by lipopolysaccharide (LPS). First, LPS increased UCP2 expression in cardiomyocytes in a time-dependent manner. LPS increased the production of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and malondialdehyde (MDA) and decreased the level of superoxide dismutase (SOD). However, UCP2 knockdown increased the LPS-induced cardiac injury and oxidative stress. In addition, LPS damaged the mitochondrial ultrastructure and led to the disruption of mitochondrial membrane potential (MMP), as well as the release of mitochondrial cytochrome c. UCP2 knockdown aggravated mitochondrial injury and the release of mitochondrial cytochrome c. LPS increased the protein levels of Bax and cleaved-caspase-3, decreased the protein level of Bcl-2, and upregulated the protein level of mitogen-activated protein kinase. However, upon UCP2 knockdown, the protein levels of Bax and cleaved-caspase-3 increased even further, and the protein level of Bcl-2 was further decreased. The protein level of phosphorylated p38 was also further enhanced. Thus, UCP2 protects against LPS-induced oxidative stress and apoptosis in cardiomyocytes.

scholarly journals Milk-derived exosomes (MDEs) have a different biological effect on normal fetal colon epithelial cells compared to colon tumor cells in a miRNA-dependent manner

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Shimon Reif ◽  
Yaffa Elbaum Shiff ◽  
Regina Golan-Gerstl
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Human Milk ◽  
Tumor Cells ◽  
Expression Profiles ◽  
Biological Effects ◽  
Biologically Active ◽  
Type I ◽  
Dependent Manner ◽  
Mesenchymal Transformation

Abstract Background Breastfeeding is the ideal source of infant nutrition. Human milk consists not only of nutrients but also biologically active components. Among these latter compounds, exosomes contain proteins, lipids, mRNAs and miRNAs. Methods To elucidate the biological effects of milk-derived exosomes (MDEs) on normal colonic epithelial cells compared to colonic tumor cells, we incubated cells with MDEs. MDEs were able to enter into normal and tumor cells and change their miRNA expression profiles. Proliferation, cell morphology and protein expression were analyzed in these cells. Results Human milk-derived exosomes induced proliferation- and epithelial mesenchymal transformation-related changes, such as collagen type I and twist expression, in normal but not in tumor cells. PTEN, a target of miRNA-148a, was downregulated in normal but not in tumor cells following incubation with MDEs. Moreover, miRNA-148a-3p knockdown cells were used to demonstrate the importance of miRNA in the effect of exosomes on cell proliferation and protein expression. MDEs inhibited proliferation and DNMT1 expression in cells with knockdown of miRNA-148a. Conclusions In conclusion, the positive effect of exosomes on normal cells without affecting tumor cells may presents an aspect of their safety when considering it use as a nutritional supplement to infant formula.

scholarly journals Spatiotemporal Protein Expression Profiles of QSOX1 in the Murine Uterus, Placenta, and Embryo during Pregnancy

2021 ◽  
Vol 11 (21) ◽  
pp. 10151
Author(s):  
Hung-Shih Lin ◽  
Robert Kuo-Kuang Lee ◽  
Tsung-Hsien Yang ◽  
Hsu-Wei Fang ◽  
Sheng-Hsiang Li
Keyword(s):  
Protein Expression ◽  
Expression Profiles ◽  
Sulfhydryl Group ◽  
Vomeronasal Organ ◽  
Cellular Protein ◽  
Thoracic Vertebrae ◽  
Pregnant Uterus ◽  
Protein Levels ◽  
Chorionic Plate ◽  
Protein Expression Profiles

Quiescin Q6 sulfhydryl oxidase 1 (QSOX1) catalyzes the oxidation of the sulfhydryl group to disulfide bond and is widely expressed in various tissues. This study focuses on investigating QSOX1′s spatiotemporal and cellular protein expression profile of the pregnant uterus, placenta, and developing embryo during mouse pregnancy. Immunohistochemical staining was used to reveal the localization of QSOX1 protein, and HistoQuest was applied to quantify protein levels. The expression level of QSOX1 in the decidua and muscle cells of the pregnant uterus fluctuated dramatically during pregnancy. QSOX1 was ubiquitously expressed in the labyrinth, junction zone, and chorionic plate in the placenta. The quantitative analysis found that this protein was highly expressed in the spinal cord, lens, midbrain, cerebellum, medulla oblongata, and tooth of mouse embryos, followed by the heart, intercostal muscle, diaphragm, intermediate zone, extrinsic ocular muscle, spine, pons, epidermis, tongue, ganglion, vomeronasal organ, thoracic vertebrae, and thymus. Interestingly, QSOX1 was also markedly expressed in olfactory system tissues. This comprehensive spatiotemporal study of QSOX1 protein expression will provide a basis for further investigations of the QSOX1 physiological function in the pregnant uterus, placenta, and developing embryo.

scholarly journals Prostaglandin E1 Attenuates Post-Cardiac Arrest Myocardial Dysfunction via Inhibiting Mitochondria-Mediated Cardiomyocyte Apoptosis

2020 ◽  
Author(s):  
Chenglei Su ◽  
Xinhui Fan ◽  
Feng Xu ◽  
Jiali Wang ◽  
Yuguo Chen
Keyword(s):  
Cardiac Arrest ◽  
Cytochrome C ◽  
Rat Model ◽  
Prostaglandin E1 ◽  
Caspase 3 ◽  
Myocardial Dysfunction ◽  
Cardiomyocyte Apoptosis ◽  
H9c2 Cells ◽  
Protein Levels ◽  
Mptp Opening

Abstract Background: Post-cardiac arrest myocardial dysfunction (PAMD) is a leading cause of death in resuscitated patients after cardiac arrest (CA). Prostaglandin E1 (PGE1) is a clinical drug used to mitigate ischemia injury. However, its effect on PAMD remains unknown. Methods: We investigated the protective effects of PGE1 on PAMD in a rat model of cardiac arrest and a hypoxia-reoxygenation (H/R) H9c2 cell model. Forty-two male Wistar rats were randomly assigned to CA, CA+PGE1, and sham groups. Asphyxia for 8 min followed by cardiopulmonary resuscitation was performed in the CA and CA+PGE1 groups. PGE1 (1 μg/kg) was intravenously administered at the onset of return of spontaneous circulation (ROSC). Ejection fraction (EF) and cardiac output (CO) were measured at baseline, 1, 2, 3, and 4 h after ROSC; survival was monitored for 72 h. Cardiomyocyte apoptosis, mitochondrial permeability transition pore (mPTP) opening, and protein levels of glycogen synthase kinase 3β (GSK3β), cytochrome c, and cleaved caspase-3 were measured 4 h after ROSC. H9c2 cells were treated with PGE1(0.5 μM) at the start of reoxygenation. Apoptosis, mPTP opening, and protein levels of GSK3β, cytochrome c, and cleaved caspase-3 of H9c2 cells were detected. Results: Compared to the CA group, PGE1 treatment significantly increased the EF and CO within 4 h after ROSC and improved the survival rate. It activated GSK3β, prevented mPTP opening, suppressed cytochrome c and cleaved caspase-3 expression, and reduced cardiomyocyte apoptosis in the rat model. In vitro, Changes in GSK3β, mPTP opening, cytochrome c and cleaved caspase-3 expression, and apoptosis in H9c2 cells were consistent with those in the rat model. Conclusions: Our results indicate that PGE1 attenuates PAMD via inhibiting mitochondria-mediated cardiomyocyte apoptosis.

scholarly journals An assessment of the multifactorial profile of steroid-metabolizing enzymes and steroid receptors in the eutopic endometrium during moderate to severe ovarian endometriosis

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
G. Anupa ◽  
Jai Bhagwan Sharma ◽  
Kallol K. Roy ◽  
Jayasree Sengupta ◽  
Debabrata Ghosh
Keyword(s):  
Menstrual Cycle ◽  
Steroid Receptors ◽  
Expression Profiles ◽  
Proof Of Concept ◽  
Secretory Phase ◽  
Tissue Concentrations ◽  
Ovarian Endometriosis ◽  
Metabolizing Enzymes ◽  
Eutopic Endometrium ◽  
Protein Levels

Abstract Background Previous studies of expression profiles of major endometrial effectors of steroid physiology in endometriosis have yielded markedly conflicting conclusions, presumably because the relative effects of type of endometriosis, fertility history and menstrual cycle phases on the measured variables were not considered. In the present study, endometrial mRNA and protein levels of several effectors of steroid biosynthesis and action in patients with stage III-IV ovarian endometriosis (OE) with known fertility and menstrual cycle histories were compared with the levels in control endometrium to test this concept. Methods Endometrial samples were collected from patients without endometriosis (n = 32) or OE stages III-IV (n = 52) with known fertility and cycle histories. qRT-PCR and immunoblotting experiments were performed to measure levels of NR5A1, STAR, CYP19A1, HSD17Bs, ESRs and PGR transcripts and proteins, respectively. Tissue concentrations of steroids (P4, T, E1 and E2) were measured using ELISAs. Results The levels of expression of aromatase and ERβ were lower (P < 0.0001) and 17β-HSD1 (P < 0.0001) and PRA (P < 0.01) were higher in OE endometrium. Lower aromatase levels and higher 17β-HSD1 levels were detected in fertile (aromatase: P < 0.05; 17β-HSD1: P < 0.0001) and infertile (aromatase: P < 0.0001; 17β-HSD1: P < 0.0001) OE endometrium than in the matched control tissues. Both proliferative (PP) and secretory (SP) phase OE samples expressed aromatase (P < 0.0001) and ERβ (PP: P < 0.001; SP: P < 0.01) at lower levels and 17β-HSD1 (P < 0.0001) and PRA (PP: P < 0.01; SP: P < 0.0001) at higher levels than matched controls. Higher 17β-HSD1 (P < 0.01) and E2 (P < 0.05) levels and a lower (P < 0.01) PRB/PRA ratio was observed in infertile secretory phase OE endometrium than in control. Conclusions We report that dysregulated expression of 17β-HSD1 and PGR resulting in hyperestrogenism and progesterone resistance during the secretory phase of the menstrual cycle, rather than an anomaly in aromatase expression, was the hallmark of eutopic endometrium from infertile OE patients. Furthermore, the results provide proof of concept that the fertility and menstrual cycle histories exerted relatively different effects on steroid physiology in the endometrium from OE patients compared with the control subjects.

Estradiol upregulates mesangial cell MMP-2 activity via the transcription factor AP-2

2002 ◽  
Vol 282 (1) ◽  
pp. F164-F169 ◽  
Author(s):  
Michael Guccione ◽  
Sharon Silbiger ◽  
Jun Lei ◽  
Joel Neugarten
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Protein Expression ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Binding Activity ◽  
Dependent Manner ◽  
Protein Levels ◽  
Dna Binding Activity ◽  
Metalloproteinase Activity

The accumulation of extracellular matrix in the glomerular mesangium reflects the net balance between the synthesis and degradation of matrix components. We have shown that estradiol suppresses the synthesis of types I and IV collagen by cultured mesangial cells (Kwan G, Neugarten J, Sherman M, Ding Q, Fotadar U, Lei J, and Silbiger S. Kidney Int 50: 1173–1179, 1996; Neugarten J, Acharya A, Lei J, and Silbiger S. Am J Physiol Renal Physiol 279: F309–F318, 2000; Neugarten J, Medve I, Lei J, and Silbiger SR. Am J Physiol Renal Physiol 277: F1–F8, 1999; Neugarten J and Silbiger S. Am J Kidney Dis 26: 147–151, 1995; Silbiger S, Lei J, and Neugarten J. Kidney Int 55: 1268–1276, 1998; Silbiger S, Lei J, Ziyadeh FN, and Neugarten J. Am J Physiol Renal Physiol 274: F1113–F1118, 1998). In the present study, we evaluated the effects of sex hormones on the activity of matrix metalloproteinase-2 (MMP-2) in murine mesangial cells, the synthesis of which is regulated by the transcription factor activator protein-2 (AP-2). Estradiol stimulated MMP-2 activity by increasing MMP-2 protein levels in a dose-dependent manner. These effects occurred at physiological concentrations of estradiol and were receptor mediated. Estradiol also increased AP-2 protein levels and increased binding of mesangial cell nuclear extracts to an AP-2 consensus binding sequence oligonucleotide. The ability of estradiol to increase AP-2 protein expression, AP-2/DNA binding activity, MMP-2 protein expression, and metalloproteinase activity was reversed by PD-98059, a selective inhibitor of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling cascade. We conclude that estradiol upregulates the MAPK cascade, which in turn stimulates the synthesis of AP-2 protein. The resultant increased AP-2/DNA binding activity leads to increased synthesis of MMP-2 and increased metalloproteinase activity. Stimulation of metalloproteinase activity by estradiol may contribute to the protective effect of female gender on renal disease progression.

scholarly journals Sesquiterpene Lactones Inhibit Advanced Oxidation Protein Product-Induced MCP-1 Expression in Podocytes via an IKK/NF-κB-Dependent Mechanism

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yan Zhao ◽  
Si-jia Chen ◽  
Jian-cheng Wang ◽  
Hong-xin Niu ◽  
Qian-qian Jia ◽  
...  
Keyword(s):  
Protein Expression ◽  
Sesquiterpene Lactones ◽  
Advanced Oxidation ◽  
Protein Product ◽  
Renal Diseases ◽  
Dependent Manner ◽  
Protein Levels ◽  
Tanacetum Parthenium ◽  
Mrna And Protein Expression ◽  
Anti Inflammatory

Inflammation is a relevant factor in the pathogenesis of diabetes nephropathy (DN). Sesquiterpene lactones (SLs), originally isolated fromTanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN. To determine whether advanced oxidation protein products (AOPPs) can induce the expression of chemokine monocyte chemoattractant protein- (MCP-) 1 in cultured mouse podocytes and to explore the mechanisms of the potential renoprotection of SLs, we treated podocytes with AOPPs and SLs (parthenolide and its derivatives micheliolide, compound 1, and compound 2). MCP-1 mRNA and protein expression were tested using quantitative real-time PCR and ELISA, respectively, and the protein levels of IKKβ, phospho-IKKβ, IκBα, NF-κB p65, phospho-NF-κB p65, and tubulin were analyzed by Western blotting. AOPPs activated the expression of MCP-1 mRNA and protein in a dose- and time-dependent manner, activated IKKβand NF-κB p65, and promoted IκBαdegradation. The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression. Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβand NF-κB p65 phosphorylation and IκBαdegradation. Taken together, these findings provide a novel explanation for the anti-inflammatory effects of SLs that will ultimately benefit DN and potentially other inflammatory and immune renal diseases.

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