PO-165 Effects of Living-High Training-Low on HIF-1α Transcriptional Regulatory Factors MAPKs mRNA in Gastrocnemius of Rats

Objective To evaluate the effects of Living-High Training-Low on HIF-1α transcriptional regulatory factors MAPKs mRNA in gastrocnemius of Rats. Methods After adaptive training, 40 8-weeks-old male SD rats were divided into living-low quiet control group (LC), living-low training-low group (LoLo), living-high quiet control group (HC), living-high training-low group (HiLo). All living-high groups stayed in the environment with 13.6% oxygen concentration, about altitude of 3500 m, for 12h/day. All training groups underwent treadmill training with 35m/min for 1hour/day, 5days/week. 4 weeks later, the gastrocnemius was sampled 24 hours after the last training. The ERK, p38MAPK, JNK and HIF-1α mRNA genes expressions in gastrocnemius were measured by real-time quantitative PCR. Results The gastrocnemius ERK mRNA of HiLo group was significantly higher than LC (P<0.01), LoLo and HC groups (P<0.05). The p38MAPK mRNA of HiLo group was significantly higher than LC and LoLo groups (P<0.01 and P<0.05), and there was no significant difference between HiLo and HC group (P>0.05). The JNK and HIF-1α mRNA of HiLo group were significantly higher than other groups (P<0.01). Conclusions Living-High Training-Low significantly raise ERK、p38MAPK、JNK and HIF-1α gene expression in gastrocnemius of Rats. ERK, p38MAPK and JNK may be one of the transcription factors regulating HIF-1α mRNA expression in Living-High Training-Low in gastrocnemius of Rats.

Download Full-text

mRNA Expression of CYP2E1, CYP2A19, CYP1A2, HSD3B, SULT1A1 and SULT2A1 genes in surgically castrated, immunologically castrated, entire male and female pigs and correlation with androstenone, skatole, indole and Improvac-specific antibody levels

Czech Journal of Animal Science ◽

10.17221/159/2018-cjas ◽

2019 ◽

Vol 64 (No. 2) ◽

pp. 89-97

Author(s):

A. Kubešová ◽

K. Šťastný ◽

M. Faldyna ◽

Z. Sládek ◽

I. Steinhauserová ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Mrna Level ◽

Boar Taint ◽

Control Group ◽

Mrna Levels ◽

Large White ◽

Specific Antibodies ◽

Significant Difference ◽

Entire Male

This study aimed to obtain a comprehensive look at the influence of castration on mRNA expression of the genes CYP2E1, CYP1A2, CYP2A19, HSD3B, SULT2A1 and SULT1A1 and their correlation with boar taint compounds (androstenone, skatole and indole) and Improvac-specific antibodies in a Czech commercial hybrid (Large White × Landrace (sow) × Duroc (boar)). Pigs were divided into groups of entire male pigs (NC), pigs castrated surgically (SC), pigs immunologically castrated and slaughtered 8 weeks (IM8) or 15 weeks (IM15) after the second dose of Improvac, and gilts (GI). Hepatic mRNA expression, measured by quantitative real-time polymerase chain reaction, differed significantly between the control group (entire male pigs) and all groups of interest for CYP2E1, CYP1A2 and CYP2A19. The mRNA level of the HSD3B gene differed significantly between the control group and the IM8, IM15 and GI groups. SULT1A1 gene expression was significantly different between the control group and the SC, IM8 and GI. In the case of SULT2A1, a significant difference was observed only between the control group and IM8 pigs. For all genes and treatment groups described above, expression was increased relative to the control. Significant differences for Improvac-specific antibodies between IM8 and IM15 groups were observed, indicating decrease of antibodies over time. Moreover, negative correlations between androstenone and mRNA levels of CYP2A19, CYP2E1 and SULT1A1 suggest that gene expression is suppressed.

Download Full-text

ATF4, DLX3, FRA1, MSX2, C/EBP-ζ, and C/EBP-α Shape the Molecular Basis of Therapeutic Effects of Zoledronic Acid in Bone Disorders

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200721101904 ◽

2020 ◽

Vol 20 (18) ◽

pp. 2274-2284

Author(s):

Faroogh Marofi ◽

Jalal Choupani ◽

Saeed Solali ◽

Ghasem Vahedi ◽

Ali Hassanzadeh ◽

...

Keyword(s):

Gene Expression ◽

Zoledronic Acid ◽

Mrna Expression ◽

Promoter Methylation ◽

Methylation Level ◽

Target Genes ◽

Osteoblastic Differentiation ◽

Therapeutic Effects ◽

Significant Difference ◽

Scheduled Time

Objective: Zoledronic Acid (ZA) is one of the common treatment choices used in various boneassociated conditions. Also, many studies have investigated the effect of ZA on Osteoblastic-Differentiation (OSD) of Mesenchymal Stem Cells (MSCs), but its clear molecular mechanism(s) has remained to be understood. It seems that the methylation of the promoter region of key genes might be an important factor involved in the regulation of genes responsible for OSD. The present study aimed to evaluate the changes in the mRNA expression and promoter methylation of central Transcription Factors (TFs) during OSD of MSCs under treatment with ZA. Materials and Methods: MSCs were induced to be differentiated into the osteoblastic cell lineage using routine protocols. MSCs received ZA during OSD and then the methylation and mRNA expression levels of target genes were measured by Methylation Specific-quantitative Polymerase Chain Reaction (MS-qPCR) and real.time PCR, respectively. The osteoblastic differentiation was confirmed by Alizarin Red Staining and the related markers to this stage. Results: Gene expression and promoter methylation level for DLX3, FRA1, ATF4, MSX2, C/EBPζ, and C/EBPa were up or down-regulated in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21. ATF4, DLX3, and FRA1 genes were significantly up-regulated during the OSD processes, while the result for MSX2, C/EBPζ, and C/EBPa was reverse. On the other hand, ATF4 and DLX3 methylation levels gradually reduced in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21, while the pattern was increasing for MSX2 and C/EBPa. The methylation pattern of C/EBPζ was upward in untreated groups while it had a downward pattern in ZA-treated groups at the same scheduled time. The result for FRA1 was not significant in both groups at the same scheduled time (days 0-21). Conclusion: The results indicated that promoter-hypomethylation of ATF4, DLX3, and FRA1 genes might be one of the mechanism(s) controlling their gene expression. Moreover, we found that promoter-hypermethylation led to the down-regulation of MSX2, C/EBP-ζ and C/EBP-α. The results implicate that ATF4, DLX3 and FRA1 may act as inducers of OSD while MSX2, C/EBP-ζ and C/EBP-α could act as the inhibitor ones. We also determined that promoter-methylation is an important process in the regulation of OSD. However, yet there was no significant difference in the promoter-methylation level of selected TFs in ZA-treated and control cells, a methylation- independent pathway might be involved in the regulation of target genes during OSD of MSCs.

Download Full-text

Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

Journal of Neural Transmission ◽

10.1007/s00702-021-02374-4 ◽

2021 ◽

Author(s):

Frank Faltraco ◽

Denise Palm ◽

Adriana Uzoni ◽

Lena Borchert ◽

Frederick Simon ◽

...

Keyword(s):

Gene Expression ◽

Dermal Fibroblast ◽

Sleep Onset ◽

Dermal Fibroblasts ◽

Control Group ◽

Adhd Group ◽

Healthy Controls ◽

Circadian Gene ◽

Significant Difference ◽

Circadian Preference

AbstractA link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.

Download Full-text

Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽

10.3390/molecules26020331 ◽

2021 ◽

Vol 26 (2) ◽

pp. 331

Author(s):

Jung-Yun Lee ◽

Tae Yang Kim ◽

Hanna Kang ◽

Jungbae Oh ◽

Joo Woong Park ◽

...

Keyword(s):

Gene Expression ◽

Body Weight ◽

Density Lipoprotein ◽

Treated Group ◽

Control Group ◽

Chitosan Oligosaccharide ◽

Sd Rats ◽

Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

Download Full-text

Cholesterol Transporters ABCA1 and ABCG1 Gene Expression in Peripheral Blood Mononuclear Cells in Patients with Metabolic Syndrome

Cholesterol ◽

10.1155/2015/682904 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 12

Author(s):

Zahra Tavoosi ◽

Hemen Moradi-Sardareh ◽

Massoud Saidijam ◽

Reza Yadegarazari ◽

Shiva Borzuei ◽

...

Keyword(s):

Gene Expression ◽

Metabolic Syndrome ◽

Mononuclear Cells ◽

Fasting Blood Glucose ◽

Control Group ◽

Regulation Mechanism ◽

Healthy Individuals ◽

Peripheral Blood Mononuclear ◽

Significant Difference ◽

Abca1 Expression

ABCA1 and ABCG1 genes encode the cholesterol transporter proteins that play a key role in cholesterol and phospholipids homeostasis. This study was aimed at evaluating and comparing ABCA1 and ABCG1 genes expression in metabolic syndrome patients and healthy individuals. This case-control study was performed on 36 patients with metabolic syndrome and the same number of healthy individuals in Hamadan (west of Iran) during 2013-2014. Total RNA was extracted from mononuclear cells and purified using RNeasy Mini Kit column. The expression of ABCA1 and ABCG1 genes was performed by qRT-PCR. Lipid profile and fasting blood glucose were measured using colorimetric procedures. ABCG1 expression in metabolic syndrome patients was significantly lower (about 75%) compared to that of control group, while for ABCA1 expression, there was no significant difference between the two studied groups. Comparison of other parameters such as HDL-C, FBS, BMI, waist circumference, and systolic and diastolic blood pressure between metabolic syndrome patients and healthy individuals showed significant differences (P<0.05). Decrease in ABCG1 expression in metabolic syndrome patients compared to healthy individuals suggests that hyperglycemia, related metabolites, and hyperlipidemia over the transporter capacity resulted in decreased expression of ABCG1. Absence of a significant change in ABCA1 gene expression between two groups can indicate a different regulation mechanism for ABCA1 expression.

Download Full-text

Laser Speckle Imaging of Sensitized Acupoints

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/7308767 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Ning Ding ◽

Jing Jiang ◽

Xiaoxiao Liu ◽

Yiyuan Xu ◽

Jiatong Hu ◽

...

Keyword(s):

Blood Perfusion ◽

Laser Speckle ◽

Control Group ◽

Functional Changes ◽

Pathological Conditions ◽

Sd Rats ◽

Significant Difference ◽

Group A ◽

Severity Of The Disease ◽

Group B

Acupoints microcirculatory dynamics vary depending on the body’s health status. However, the functional changes observed during acupoint sensitization, that is, the disease-induced change from a “silenced” to an “activated” status, remain elusive. In this study, the microcirculatory changes at acupoints during sensitization were characterized. Thirty SD rats were randomly divided into five groups: normal control group (N), sham osteoarthritis group (S), light osteoarthritis group (A), mild osteoarthritis group (B), and heavy osteoarthritis group (C). The obtained results showed that the blood perfusion levels at the acupoints Yanglingquan (GB34), Zusanli (ST36), and Heding (EX-LE2) in groups A, B, and C were higher than those in groups N and S on days 14, 21, and 28 (p < 0.01 or p < 0.05). A significant difference in the blood perfusion was also observed at the acupoint Weizhong (BL40) in groups B and C on days 21 and 28 (p < 0.01). In addition, remarkable differences in the level of blood perfusion at the GB34, ST36, and EX-LE2 acupoints were observed on day 28 (p < 0.01 or p < 0.05) among groups A, B, and C. No marked differences in blood perfusion levels were observed at the nonacupoint site among all groups. In conclusion, acupoint sensitization is associated with an increase in the level of local blood perfusion at specific acupoints, and this increase is positively correlated with the severity of the disease. The functional changes in microcirculation at acupoints during sensitization reflect the different physiological and pathological conditions imposed by the disease.

Download Full-text

Abstract 14356: Blood Tests That Improve the Accuracy of a Brugada Syndrome Diagnosis

Circulation ◽

10.1161/circ.132.suppl_3.14356 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Anyu Zhou ◽

Ning Jinag ◽

Marco Denegri ◽

An Xie ◽

Guangbin Shi ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Brugada Syndrome ◽

Roc Analysis ◽

White Blood Cells ◽

Control Group ◽

Mrna Levels ◽

Operating Characteristics ◽

Optimal Cutoff ◽

Scn5a Mutation

Objectives: To discover the role of altered gene expression regulation in Brugada Syndrome (BrS) and to find biomarkers for BrS diagnosis. Methods: Twenty-five control patients (Control), 25 BrS patients without SCN5A mutation (SCN5A(-)) and 20 BrS patients with SCN5A mutation (SCN5A(+)) were included in this study. Specified gene expression of white blood cells (WBC) were measured by RT-qPCR using TaqMan® Gene Expression assay. Results: MEF2C and MESP1 are the two major cardiac specific transcription factors expressed in WBC. The mRNA expression levels of SCN5A, MEF2C and HuR, one of mRNA stabilizers, were decreased in the SCN5A (+) group (P=0.047, 0.02, 0.000 vs. control group, respectively). The mRNA expression of MESP1 in WBCs was significantly lower in both SCN5A(-) (P=0.012 vs. control) and SCN5A(+) (P=0.000 vs. control) groups. There was no difference between the two BrS groups in MESP1 expression (P=0.215). The area under the Receiver Operating Characteristics (ROC) analysis curve for prediction of BrS using MESP1 levels was 0.775 (95% CI 0.668, 0.882, asymptotic Sig.=0.000). At the optimal cutoff, the corresponding maximum sensitivity and specificity were 0.62 (95% CI: 0.47, 0.76) and 0.88 (0.69, 0.97), respectively. The diagnostic odds ratio (DOR) of MESP1 for BrS diagnosis was 11.96 (95% CI: 5.79, 24.73). The assessment of the mRNA levels in blood SCN5A, MEF2C and HuR were useful for predicting BrS patients with an SCN5A mutation. The area under the ROC analysis curve for prediction of BrS with an SCN5A mutation using SCN5A, MEF2C and HuR mRNA levels in WBCs was 0.847 (95% CI 0.752, 0.942, asymptotic Sig.=0.000), 0.685 (95% CI 0.542, 0.828, asymptotic Sig.=0.016) and 0.777 (95% CI 0.652, 0.902, asymptotic Sig.=0.000), respectively. At the optimal cutoff, the DOR of SCN5A, MEF2C and HuR for SCN5A(+) BrS diagnosis was 17.5 (95% CI: 8.06, 37.86), 4.9 (95% CI: 2.61, 9.17) and 23.5 (95% CI: 9.39, 58.80), respectively. Conclusions: Our results suggest that assessment of circulating MESP1 may be used as a biomarker for BrS diagnosis while decreased SCN5A, MEF2C and HuR mRNA in WBCs is associated with BrS patients with an SCN5A mutation. Our results also suggest that decreased expression of SCN5A, MEF2C, MESP1, and HuR may be pathophysiologically related to BrS.

Download Full-text

Investigation of TAp63 gene Expression and Follicle Count Using Melatonin in Cisplatin-induced Ovarian Toxicity

10.21203/rs.3.rs-52313/v1 ◽

2020 ◽

Author(s):

Hacı Öztürk Şahin ◽

Mehmet Nuri Duran ◽

Fatma Sılan ◽

Ece Sılan ◽

Duygu Sıddıkoglu ◽

...

Keyword(s):

Gene Expression ◽

Female Rats ◽

Histological Evaluation ◽

Saline Control ◽

Control Group ◽

Ovarian Toxicity ◽

Significant Difference ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Background: Premature ovarian failure is among the most important side effects of chemotherapy during reproductive period. Preserving ovarian function is gradually gaining importance during oncologic treatment. The present study aims to investigate the potential of melatonin to protect from cisplatin-induced ovarian toxicity in rats. Twenty nine female rats were divided to three groups: Saline control group (Group 1), cisplatin group (Group 2), and cisplatin+melatonin group (Group 3). While the rats in Groups 2 and 3 were administered 5 mg/kg single dose of cisplatin via intra-peritoneal (IP) route, the rats in Group 3 were started on melatonin (20 mg/kg IP) before cisplatin administration and continued during 3 consecutive days. Ovaries were removed one week after cisplatin administration in all groups. Blood samples were obtained before the rats were decapited. Histological evaluation, follicle count, and classification were performed. TAp63 mRNA expression was evaluated using mRNA extraction and real-time polymerase chain reaction (PCR) method. Serum estradiol (E2) and anti-mullerian hormone (AMH) values were measured with enzyme immune-assay technology. Results: While primordial follicles were seen to decrease in Group 2 as compared to Group 1 (p:0.023), primordial follicle count was observed to be preserved significantly in melatonin group as compared to Group 2 (p:0.047). Moreover, cisplatin-induced histo-pathological morphology was preserved in favor of normal histology in melatonin group. A significant difference was not observed between groups with regard to mean serum AMH and E2 values (p:0.102 and p:0.411, respectively). While TAp63 gene expression significantly increased in Group 2 as compared to control group (p:0.001), we did not detect a statistically significant difference in cisplatin+melatonin group, although gene expression decreased (p:0.34). Conclusion: We conclude that concurrent administration of melatonin and cisplatin may protect from ovarian damage.

Download Full-text

P3486Experimental model for heart failure in rats: apelin-13/apj and bnp-45 gene expression analysis

European Heart Journal ◽

10.1093/eurheartj/ehz745.0354 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H R Helmi ◽

A P Sunjaya ◽

D Limanan ◽

A R Prijanti ◽

S W A Jusman ◽

...

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Cardiac Hypertrophy ◽

Mrna Expression ◽

Rat Model ◽

Control Group ◽

P Value ◽

Sprague Dawley ◽

Hypoxia Exposure ◽

Systemic Hypoxia

Abstract Background Apelin, an adipokine peptide and its receptor has recently emerged as a key signaling pathway in maintaining cardiac performance at chronic pressure loads. Apelin has been linked to ventricular dysfunction and therefore maybe of pathophysiologic relevance as a candidate biomarker in HF patients. Purpose This study aims to investigate Apelin-13 gene expression and level, and Apelin receptor (APJ) level in a rat model of heart failure induced by chronic systemic hypoxia and their correlation to BNP-45 gene expression and level, the current gold standard biomarker for heart failure, and to cardiac histopathologic changes. The effect of chronic systemic hypoxia on cardiac hypertrophy, remodeling and heart failure parameters is also of interest. Methods Twenty-eight male Sprague-Dawley rats (8–12 weeks of age) were placed in special hypoxic chambers divided into 7 groups – a control group provided with normoxia (atmospheric O2 levels) and 6 exposure groups exposed to hypoxia (8% O2) for 6 hours, 1, 3, 5, 7 and 14 days respectively prior to measurement. Changes in the expression of Apelin and BNP-45 were measured using quantitative real-time PCR, whereas changes in Apelin-13, APJ and BNP-45 levels were measured using ELISA. Histopathology staining using Hematoxylin and Eosin was performed on cardiac tissues post-termination. Results Compared to control, BNP-45 mRNA expression in the hypoxic heart was only significantly different in day 14, whereas, Apelin mRNA expression had showed significantly higher values starting from day 7 onward. This is in line with the evidence of cardiac hypertrophy based on histopathologic examination present from day 7 onwards. BNP-45 and Apelin-13 levels were significantly higher compared to control from day 5 onwards with a peak on day 7. Although significantly higher than control, Apelin-13 and BNP-45 level decreases in day 14 as compared to day 7. Mean APJ levels showed a similar profile with Apelin-13 and BNP-45 levels with a peak in day 7 (4.619 ng/mL). The cardiac Apelin-13 level shows strong significant correlation with BNP-45 levels (r 0.823, p-value 0.0001). There was also a strong significant correlation between APJ receptor levels with Apelin-13 (r 0.9029, p-value 0.001) and BNP-45 (r 0.9062, p-value 0.0009) levels. Apelin-13, APJ and BNP-45 levels also showed strong significant positive correlation to the duration of hypoxia exposure. Conclusion Chronic (≥5 days) and not acute systemic hypoxia in an experimental rat model leads to increase in Apelin-13, APJ and BNP-45 levels. Apelin-13 and BNP-45 were found to significantly increase from 5 days onwards. Apelin mRNA expression was found to show significant increase earlier compared to BNP-45 mRNA expression. Hence, Apelin may serve as a new candidate biomarker for detection of HF due to oxidative stress compared to BNP-45. Exposure to chronic systemic hypoxia can serve as an easily replicable rat model for heart failure. Acknowledgement/Funding Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia

Download Full-text

Letrozole-Induced Polycystic Ovary Syndrome Attenuates Cystathionine-β Synthase Gene Expression in the Ovaries of Female Sprague Dawley Rats

Current Developments in Nutrition ◽

10.1093/cdn/nzaa058_002 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1244-1244

Author(s):

Amanda Bries ◽

Joe Webb ◽

Brooke Vogel ◽

Claudia Carrillo ◽

Aileen Keating ◽

...

Keyword(s):

Gene Expression ◽

Polycystic Ovary Syndrome ◽

Mrna Expression ◽

Polycystic Ovary ◽

Elevated Serum ◽

Reproductive Age ◽

Sprague Dawley ◽

Polycystic Ovaries ◽

Ovary Syndrome ◽

Sd Rats

Abstract Objectives Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 10% of reproductive age women and leads to hyperandrogenism, abnormal menstrual cycles, and polycystic ovaries. Moreover, PCOS has been associated with elevated serum homocysteine; however, the characterization of one-carbon metabolism (OCM) in PCOS remains incomplete. The aim of our research was to examine OCM in a genetic and chemically-induced rodent model of PCOS: 1) viable yellow Agouti (Avy) mice; and 2) letrozole (Let)-induced Sprague Dawley (SD) rats. Methods Five wk old female Avy mice (N = 18), their lean controls (N = 18), and SD rats (N = 36) were acclimated for one wk. Following acclimation, the animals were placed on a modified standard AIN93G diet (energy, %: 50.4, carbohydrate; 17.3, protein; and 32.3, fat). Rats were randomly assigned to Let (1 g/kg BW) treatment or vehicle (carboxymethylcellulose) control that was administered via a subcutaneously implanted slow-release pellet every 30-d. For both models, 12 animals were randomly assigned to be euthanized during proestrus at one of the following ages: 8, 16 or 24 wk. Bodyweight and estrous cycles were measured daily. Ovaries were collected to assess gene expression of OCM. These data were analyzed using linear mixed models to determine the main effects of age and treatment at a significance level of P < 0.05. Results Letrozole significantly reduced the occurrence of proestrus and estrus stages (P = 0.0001 and P = 0.006, respectively). Additionally, Let-induced rats had increased BW compared to control rats, across all age groups (P < 0.0001). In contrast, Avy mice weighed less than their controls by 24 wk of age (P < 0.0001). Cystathionine-β synthase (CBS) mRNA expression was downregulated in the Let-induced vs. control rats at 16 (59%; P < 0.05) and 24 (77%; P < 0.01) wk of age. As expected, Cyp19A1, aromatase mRNA was downregulated in the Let-induced rats (P = 0.02). Interestingly, betaine-homocysteine s-methyltransferase (BHMT) mRNA increased as a function of age in Let-induced rats (P = 0.03). Conclusions These data demonstrate that Letrozole-induced PCOS temporally decreases ovarian CBS mRNA expression; whereas, BHMT mRNA is upregulated as a function of age. Funding Sources This work was supported by the National Institute of Child Health and Human Development.

Download Full-text