scholarly journals P6 Electroacupuncture Improved QTc Interval Prolongation by Upregulation of Connexin43 in Droperidol Treated Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Feng Zhao ◽  
Suyang Cui ◽  
Libing Huang
Keyword(s):  
Protein Expression ◽  
Control Group ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Cx43 Expression ◽  
Qtc Interval Prolongation ◽  
Mrna And Protein Expression ◽  
Cx43 Mrna ◽  
And Control ◽  
Group D

Aim. This study investigated the effect of P6 EA on droperidol-induced QTc interval prolongation and Cx43 expression in ventricular muscle of rats.Methods. Twenty-four rats were randomly divided into control group (C), droperidol group (D), or EA group (E). C group rats were injected with normal saline. D group rats were injected with droperidol 0.13 mg/kg. E group rats were pretreated with EA at left P6 acupoint for 30 min and then injected with droperidol (0.13 mg/kg). QTc intervals were recorded at lead II in ECG within 120 min. Cx43 expression was measured by RT-PCR and western blotting.Result. Droperidol significantly prolonged QTc intervals compared with controls at 5 min, 10 min, 15 min, and 30 min (P<0.05). P6 EA could significantly abbreviate the prolongation of QTc interval compared with droperidol group at 5 min, 10 min, 15 min, and 30 min (P<0.05). Cx43 mRNA and proteins were significantly increased by P6 EA compared with droperidol group at 120 min (P<0.05). There were no significant differences in Cx43 mRNA and protein expression between droperidol and control group at 120 min (P>0.05).Conclusion. P6 EA could improve QTc interval prolongation induced by droperidol, which may relate to upregulation of Cx43 mRNA and protein. Antiemetic dose of droperidol had minor effects on Cx43 mRNA and protein expression at 120 min.

Effects of Gingko biloba Extract on Gap Junction Changes Induced by Reperfusion/Reoxygenation After Ischemia/Hypoxia in Rat Brain

2005 ◽  
Vol 33 (06) ◽  
pp. 923-934 ◽  
Author(s):  
Zhen Li ◽  
Xian-Ming Lin ◽  
Pei-Li Gong ◽  
Fan-Dian Zeng ◽  
Guan-Hua Du
Keyword(s):  
Protein Expression ◽  
Gap Junction ◽  
Neurological Deficit ◽  
Ischemia Reperfusion ◽  
Cx43 Expression ◽  
Expression Levels ◽  
Gingko Biloba ◽  
Mrna And Protein Expression ◽  
Cx43 Mrna ◽  
Hypoxia Reoxygenation

Gap junction communication between astrocytes plays an important role in the brain. The purpose of this study was to investigate the effects of Gingko biloba extract (GBE) on the changes of connexin 43 (Cx43) mRNA and protein expression levels of rat cortex and hippocampus induced by ischemia-reperfusion and astrocyte gap junction intercellular communication (GJIC) induced by hypoxia-reoxygenation. After 2 hours of middle cerebral artery occlusion (MCAO) followed by 24 hours of reperfusion, there was obvious neurological deficit in rats. Cx43 mRNA and protein expression levels of rat cortex and hippocampus in the ischemia hemisphere were decreased significantly. When GBE at doses of 50 and 100 mg/kg body weight was administrated by p.o. daily for 7 days, the neurological deficit was improved, and lower Cx43 mRNA and protein expression levels induced by ischemia-reperfusion were recovered to normal. The i.p. injection of nimodipine (0.7 mg/kg weight body) also showed improvement on neurological deficit and Cx43 expression levels. Astrocyte GJIC was measured by the fluorescence recovery after photobleaching (FRAP). Hypoxia-reoxygenation induced a significant decrease in GJIC. Pretreatment with GBE (100 mg/l) and nimodipine (1.6 mg/l) significantly prevented the hypoxia-reoxygenation inhibition of GJIC. These results suggest that GBE could exert its neuroprotective effects by improvement of Cx43 expression and GJIC induced by hypoxia/ischemia-reoxygenation/ reperfusion injury.

scholarly journals SUZ12 Participates in PNH Cloning Proliferation By Regulating Histone H3K27me3 Methylation Level

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1106-1106
Author(s):  
Rong Fu ◽  
Yingying Chen ◽  
Zonghong Shao ◽  
Hui Liu ◽  
Lijie Zeng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Peripheral Blood ◽  
Methylation Level ◽  
Cell Model ◽  
Gene Mutations ◽  
Control Group ◽  
Mrna And Protein Expression ◽  
And Control

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a disease of hematopoietic stem cell membrane defects due to acquired PIG-Amutation. Our previous study found some secondary gene mutations in PNH patients by WES. However, it is not clear exactly which mutations are associated with the disease. So, 97 target genes were selected as a target gene panel and tested in 23 PNH patients by DNA sequencing of specific target regions. We found that all PNH patients had other gene mutations except PIG-Amutations, including TTN, NCOR2, CPS1, MUC4, SUZ12, LFNG, CELSR2, JAK2, SETBP1 and KMT2D (Figure1A). Through harmful analysis, KEGG enrichment, GO enrichment analysis and protein interaction analysis, we screened out the secondary mutant gene SUZ12 that may be involved in the cloning proliferation of PNH. We detected the mRNA and protein expression levels of SUZ12 and H3K27me3 methylation in PNH patients and health volunteers, the results showed that the mRNA and protein expression levels of SUZ12 and H3K27me3 methylation in peripheral blood CD59 -cells of PNH patients were higher than those in CD59 + cells of PNH patients and healthy controls (Figure1B). The relative expression level of SUZ12 in peripheral blood CD59 -cells of PNH patients was correlated with (r=0.4162, p=0.0385), CD59 -erythrocyte ratio (r=0.4636, p=0.0196), CD59 -monocyte ratio (r=0.4052, p=0.0495), Flaer -monocyte ratio (r=0.6769, p=0.0004) and Flaer -granulocytic ratio (r=0.6146, p=0.0018), indicating that SUZ12 may be involved in abnormal PNH cloning and proliferation by regulating H3K27me3. To verify the role of SUZ12 in the proliferation of PNH cloning, we used CRISPR/Cas9 to knockdown PIG-A expression in THP-1 cells to construct A PNH cell model, the expression level of PIG-A protein in the cell model was significantly decreased, and the proportion of CD59 - cells accounted was stable at 95%. Then lentivirus transfection was used to knockdown the expression of SUZ12 in PNH cell model. The results showed when the SUZ12 expression was knockdown, the methylation level of histone H3K27me3 was decreased, the cell proliferation activity was decreased, apoptosis was increased, and the cell cycle was arrested at G0/G1 phase. The proportion of CD59 + cells increased gradually from 3 weeks after transfection, and significantly increased at 4 weeks after transfection, while no changes were observed in the empty virus group and control group (Figure1C). Four weeks after lentivirus transfection, the expression of PIG-A protein recovered in SUZ12 knockdown group compared with empty virus group and control group (Figure1D). In conclusion, SUZ12 mutation leads to the overexpression of SUZ12, which can affect cell proliferation, apoptosis and cell cycle by regulating the methylation level of histone H3K27me3, thereby promoting the proliferation of PNH abnormal cloning and participating in the pathogenesis of PNH. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals QTc interval prolongation in asymptomatic HIV – infected patients treated and untreated with antiretroviral therapy

2019 ◽  
Vol 73 ◽  
pp. 225-231
Author(s):  
Ewa Siwak ◽  
Magdalena M. Suchacz ◽  
Iwona Cielniak ◽  
Joanna Kubicka ◽  
Piotr Pulik ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Multivariable Analysis ◽  
Antiretroviral Drugs ◽  
Control Group ◽  
Qtc Interval ◽  
Interval Duration ◽  
Interval Prolongation ◽  
Qtc Prolongation ◽  
Qtc Interval Prolongation ◽  
Asymptomatic Hiv

Aim: QTc interval prolongation has been found in HIV-infected patients. There are contradictory reports about the effects of antiretroviral drugs on QT interval duration. The aim of the study was to assess if the prolongation of the QTc interval depends on the antiretroviral treatment and other risk factors related to HIV infection. Material/Methods: 283 adult HIV-infected patients treated in HIV Outpatient Clinic in Warsaw were enrolled in the prospective, single-centre study. Factors related to ART and HIV infection were collected. Electrocardiograms were performed for each patient and QTc interval duration was measured and corrected using Bazett’s heart rate formula. Results: Prolonged QTc interval was identified in 4.9 % HIV-infected patients (median age 34.5 years, 85% male, 89% HIV RNA<50 copies/mL). The average length of QTc interval in ART HIV(+) patients was 403 ms, in untreated HIV(+) subjects – 398ms and in the control group of healthy individuals – 400ms. ART regimen included PI in 47.4% cases, NNRTI in 24.1% and INI in 28.5% patients. The longest QTc interval was found in patients treated with the PI scheme – 408 ms, shorter with INI – 399ms and with NNRTI – 397ms. A multivariable analysis revealed that only older age and female gender were significantly associated with QTc prolongation. Conclusions: In the group of young, asymptomatic HIV-infected patients with good immunovirological control, the prevalence of QTc prolongation was low – only 4.9% of subjects. ARV treatment seem to have no significant influence on the QTc interval duration.

Liraglutide Effect on Ventricular Transient Outward K +  Channel and Connexin-43 Protein Expression

2020 ◽  
Author(s):  
Nehal M. Ramadan ◽  
Hala Abdel Malek ◽  
Karawan Abd-el Rahman ◽  
Elhamy El-Kholy ◽  
Dalia Shaalan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
High Fat Diet ◽  
Connexin 43 ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Cx43 Expression ◽  
Qtc Interval Prolongation

Abstract Background Human glucagon-like peptide-1 analogue, Liraglutide, has shown cardioprotective effects in animal and clinical studies of type 2 diabetes mellitus. This study was conducted to assess the effect of Liraglutide on diabetes-induced myocardial electrical remodeling. Materials and Methods A rat model of type 2 diabetes mellitus was induced by high-fat diet and low dose Streptozotocin (35 mg/kg). Diabetic rats were randomized into 4 subgroups (n=6–7): diabetic-untreated, diabetics treated with Liraglutide, diabetics treated with Ramipril, and diabetics treated with Metformin in addition to a control group. Changes in serum glucose, insulin, lipid profile and revised quantitative insulin sensitivity check index (QUICKI index) were assessed. QT and QTc intervals were measured and the degree of cardiac interstitial and perivascular fibrosis was examined. The expression of myocardial Ito channel α subunits, gap junction protein; Kv 4.2/4.3 and connexin 43 (Cx43) respectively, were assessed by western blotting and immunohistochemistry. Results Similar to Ramipril, both Liraglutide and Metformin effectively inhibited the diabetes-induced myocardial hypertrophy and fibrosis. However, Liraglutide treatment significantly improved Kv 4.2/4.3 and Cx43 expression/distribution and prevented diabetes-related QTc interval prolongation. Conclusions We have shown that pathological alterations in myocardial Cx43 expression and distribution, in addition to reduced Ito channel expression, may underlie the QTc interval prolongation in high-fat diet/STZ rat model of type 2 diabetes mellitus. The beneficial effects of Liraglutide, as those of Ramipril, on cardiac electrophysiology could be at least attributed to its direct ability to normalize expression and distribution of Cx43 and Ito channels in the diabetic rat heart.

scholarly journals Estradiol Reduces Connexin43 Gap Junctions in the Uterus during Adenomyosis in Cows

2016 ◽  
Vol 19 (3) ◽  
pp. 609-617 ◽  
Author(s):  
A.J. Korzekwa ◽  
M. Łupicka ◽  
B.M. Socha ◽  
A.A. Szczepańska
Keyword(s):  
Protein Expression ◽  
Gap Junctions ◽  
Mrna Expression ◽  
Uterine Tissue ◽  
Cx43 Expression ◽  
Junction Protein ◽  
Uterine Adenomyosis ◽  
Mrna And Protein Expression ◽  
Gap Junction Protein ◽  
Cx43 Mrna

Abstract Adenomyosis is defined as the presence of glandular foci external to the endometrium of the uterus, either in the myometrium or/and perimetrium, depending on the progress of this dysfunction. To date, we showed that steroids secretion and prolactin expression and proliferative processes are disturbed during uterine adenomyosis in cows. During endometriosis in eutopic endometrium in women, gap junctions are down regulated. The transmembrane gap junction protein, connexin (Cx43) is necessary for endometrial morphological, biochemical and angiogenic functions. The aim of this study is recognition of adenomyosis etiology by determination of the role of Cx43 in this process. Immunolocalization and comparison of Cx43 mRNA and protein expression in healthy (N=9) and adenomyotic uterine tissue (N=9), and Cx43 mRNA expression (real time PCR) in uterine stromal – myometrium co-culture under 24-hour stimulation with 17-beta estradiol (10−7M) isolated from healthy (N=5) and adenomyotic (N=5) cows were determined. Cx43 was localized in healthy and adenomyotic uteri. mRNA and protein expression was down-regulated in uterine tissue in adenomyotic compared with healthy cows (p<0.05). Estradiol stimulated Cx43 mRNA expression in myometrial cell culture and co-culture of stromal and myometrial cells in adenomyotic compared with healthy cows (p<0.05). In summary, down-regulation of Cx43 expression in the junction zone might play an important role in pathogenesis of adenomyosis. Estradiol modulates gap junctions during adenomyosis.

scholarly journals Hyperinsulinaemic hypoglycaemia in non-anaesthetized Göttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mille K. Lyhne ◽  
Andreas Vegge ◽  
Gro Klitgaard Povlsen ◽  
Rita Slaaby ◽  
Jonas Kildegaard ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Fold Increase ◽  
Diabetic Group ◽  
Large Animal ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Large Animal Models ◽  
Qtc Interval Prolongation ◽  
Electrocardiographic Recordings

AbstractThe potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8–1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.

scholarly journals The Acute Effects of Swimming Exercise on PGC-1α-FNDC5/Irisin-UCP1 Expression in Male C57BL/6J Mice

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 111
Author(s):  
Eunhee Cho ◽  
Da Yeon Jeong ◽  
Jae Geun Kim ◽  
Sewon Lee
Keyword(s):  
Adipose Tissue ◽  
Protein Expression ◽  
Swimming Exercise ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Brown Adipose ◽  
Mrna And Protein Expression ◽  
Ucp1 Expression ◽  
Exercise Induced ◽  
Gastrocnemius Muscles

Irisin is a myokine primarily secreted by skeletal muscles and is known as an exercise-induced hormone. The purpose of this study was to determine whether the PGC-1α -FNDC5 /Irisin-UCP1 expression which is an irisin-related signaling pathway, is activated by an acute swimming exercise. Fourteen to sixteen weeks old male C57BL/6J mice (n = 20) were divided into control (CON, n = 10) and swimming exercise groups (SEG, n = 10). The SEG mice performed 90 min of acute swimming exercise, while control (non-exercised) mice were exposed to shallow water (2 cm of depth) for 90 min. The mRNA and protein expression of PGC-1α, FNDC5 and browning markers including UCP1 were evaluated by quantitative real-time PCR and western blotting. Serum irisin concentration was measured by enzyme-linked immunosorbent assay. An acute swimming exercise did not lead to alterations in the mRNA and protein expression of PGC-1α in both soleus and gastrocnemius muscles, the mRNA and protein expression of UCP1 in brown adipose tissue, mRNA browning markers in visceral adipose tissue and circulating irisin when compared with the control group. On the other hand, an acute swimming exercise led to increases in the mRNA and protein expressions of FNDC5 in the soleus muscle, the protein expression of FNDC5 in the gastrocnemius muscles and the protein expression of UCP1 in subcutaneous adipose tissue.

Sign in / Sign up

Export Citation Format

Share Document