جستجوی مقالات مرتبط با کلیدواژه « Endoplasmic Reticulum » در نشریات گروه « پزشکی »

The health and proper functioning of the endoplasmic reticulum in the liver can lead to an increase in the quality of the metabolism of liver cells. Exercise can lead to liver health by regulating liver enzymes and factors related to apoptosis pathway. Therefore, the aim of the current research is to compare the performance of the endoplasmic reticulum chaperone protein of the liver of healthy model rats with the intervention of different training sessions and starvation.

In this experimental research, 30 Wistar male rats with a weight range of 330 ± 25 grams were selected and divided into six groups: 1) control, 2) starvation, 3) 3 days of training per week, 4) 5 days of training per week, 5) starvation + 3 training days per week, 6) starvation + 5 training days per week. Training consisted of one hour of continuous running on a treadmill for 4 weeks, and starvation was performed for 14 hours when the rats were awake. Data analysis was performed using one-way analysis of variance and post hoc LSD statistical tests in SPSS version 23 software. A significance level of P≤ 0.05 was considered.

Data analysis showed a significant change in the levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST) (P≤ 0.05). This change in CHOP gene expression was also significant (P≤ 0.05).

Aerobic training for 3 and 5 days with starvation can lead to liver health by reducing liver enzymes (AST and ALT) and cell death-related factor (CHOP) through the apoptosis pathway.

Endoplasmic reticulum plays an essential role in many cellular pathways. Exercise and fasting can lead to liver health by activating mechanisms such as reticulophagy. Therefore, the aim of the current research is to  investigate the effect of fasting and aerobic exercise on atherogenic indicators, body mass and ATF6 gene expression in the endoplasmic reticulum of healthy liver of Wistar rats.

In this experimental research, 30 18-week-old Wistar rats with a weight range of 330.40 ± 25.34 grams were selected and divided into six groups: 1) control, 2) starvation, 3) 3-day training, 44) 5-day training, 5) starvation + 3-day training, 6) starvation + 5-day training were divided. The rats in the training group performed exercise on a treadmill for one month, 3 and 5 sessions per week for one hour. Starvation was done continuously for 14 hours when the rats were awake and for one month. Data analysis was done using one-way ANOVA and post hoc LSD statistical tests in SPSS version 23 software. A significance level of P≥0.05 was considered.

Data analysis showed a significant decrease in BMI, LDL/HDL, CHOL/HDL, TAG/HDL and a significant increase in ATF6 gene expression (P≥0.05).

Aerobic training with starvation led to liver health by reducing atherogenic indicators. Also, increasing the expression of ATF6 gene in the liver through exercise and starvation can lead to the regulation of reticulophagia and liver health.

Diabetes is the most prevalent endocrine disease. Apoptosis and necroptosis play a major role in the development of diabetes-related heart diseases; however, the effects of continuous and interval exercise on apoptosis and necroptosis of the heart cells in diabetics are unclear. This study aimed to investigate the effect of different intensities of aerobic exercise on apoptosis and necroptosis of the cardiac tissue of diabetic mice.

In total, 32 mature, male, and white Wistar rats (mean age of 12±2 weeks and weight of 175±15 g) were randomly divided into four groups of eight animals per group. The groups included a healthy control (C), diabetic control (D), diabetic with moderate-intensity continuous training (55 min with 26 m/min speed daily) (D+MICT), and diabetic with high-intensity interval training at the 85-90% of maximum speed (D+HIIT) (5 days/week for 8 weeks). Before the training protocol, the running speed was calculated to obtain the maximum oxygen consumption. Western blot analysis was utilized to evaluate the changes in the expression of the proteins associated with apoptosis and necroptotic death path in the diabetic heart muscle myocardium. Furthermore, the one-way analysis of variance was used to determine the differences among the study groups. A p-value less than 0.05 was considered statistically significant. Ethics code: IAU.SARI.REC.1397.8

 The results indicated that type 2 Diabetes Mellitus significantly increased both apoptotic and necroptotic cell death (P=0.001). However, both continuous and interval training moderated the apoptotic cell death (P≤0.05). Nonetheless, the effect of interval training was higher than that of the continuous one. It is worth mentioning that only interval training had a significant effect on reducing the necroptosis (P≤0.05).

 It seems that continuous and interval exercise affects apoptotic death; however, intense interval exercise is more effective in necroptotic death.

This study aimed to investigate the association between Endoplasmic Reticulum autophagy (ER-phagy) and Alzheimer’s Disease (AD) by analyzing the expression patterns of related genes in animal models.

Microarray data of AD patients’ brain tissues were extracted from the Gene Expression Omnibus (GEO) database. These data were first analyzed in GEO2R online tool. Then, the expression of ER-phagy related genes were isolated and the protein interaction networks were plotted by STRING database for the genes with increased expression. Finally, the relationship between the genes that had significant increased expression were designed, and the expression of new identified genes in each study was examined. 

 All ethical principles were considered in this article. 

 Genes involved in ER-phagy showed a sporadic expression in different AD models. An increase in the expression of ER-phagy regulatory 1 (FAM134B) gene was observed in studies with the mutation in both Microtubule-associated Protein Tau (MAPT) and Amyloid Precursor Protein (APP) genes. Increase in the expression of NPC intracellular cholesterol transporter 1 (NPC1) gene was observed in two studies that had mutations in APP, Presenilin 1 (PSEN1) and MAPT genes. Moreover, SEC62 homolog and Cell Cycle Progression 1 (CCPG1) genes both showed decreased expression in one study. Finally, the expression of Reticulon 3 (RTN3) was not significant in any of the studies.

 The genes involved in ER-phagy have a sporadic expression in AD models, where only two genes FAM134B and NPC1 are involved in AD. The FAM134B gene seems to interact with the Wnk1 gene, which plays a role in cell survival and proliferation, in the hippocampus and forebrain. It also interacts with the Map1lc3b gene, which has a role in phagosome deletion and protein ubiquitination, in the forebrain. It also interacts with the Map1lc3b gene, which has a role in phagosome deletion and protein ubiquitination, in the forebrain. NPC1 had interaction with the Abcg1 gene, which activates lipid homeostasis, in the subventricular zone.

Perturbation of endoplasmic reticulum (ER) homeostasis under a stressful situation leads to a stress condition termed “ER stress” which induces the activation of a finely regulated program defined as unfolded protein response (UPR), whose primary aim is to restore disorders or normal cell conditions. Under prolonged or sustained ER, stress conditions may result in activation-induced cell death. The UPR has three main arms; activation of each arm can lead to various effects on the expression of essential genes in cells. In recent years, ER stress response regulator molecules have been considered by the researchers as a very strong and effective candidate for pharmaceutical and therapeutic purposes in many diseases, including cancer, Alzheimer's disease, Parkinson's disease, diabetes, heart and liver diseases, and allergies.

Defects in endoplasmic reticulum (ER) homeostasis are common in different diseases, such as diabetes. It is now well established that ion channels of ER membrane have a critical role in ER luminal homeostasis. Our previous studies showed the presence of a 346 pS potassium channel in ER. Therefore, in this study, we examined and compared the activities of this channel in control and diabetic rats using single-channel recording techniques.

Diabetes mellitus was established in male Wistar rats 2 weeks after single injection of streptozotocin 45 mg/kg, i.p. Ion channel of rough endoplasmic reticulum of diabetic hepatocytes was incorporated into the bilayer lipid membrane and the characterization of K+ channel was then evaluated.

Based on our previous data, endoplasmic reticulum membrane has a potassium channel with a main conductance of 346 pS, which is sensitive to 4-Aminopyridine and voltage-insensitive at ± 30 mV. In the present study, it was demonstrated that the channel conductance was decreased to 259 pS in diabetes mellitus. Interestingly, the channel Po-voltage relation demonstrated that channel Po significantly lower in diabetic rats compared to normal rats at different voltages.

Our data showed that the biophysical properties of potassium channel were significantly altered under diabetic condition. We propose that the hepatocyte ER potassium channels are involved in diabetes pathology, and it may be considered as a target for therapeutic plans.

It has recently been suggested that the KATP channel subunits Kir6. x and BKCa channels exist in the endoplasmic reticulum of cardiomyocytes and neurons. Our previous studies showed the electrophysiological behavior of cation channels in the rough endoplasmic reticulum (RER) of rat hepatocytes. Therefore، we hypothesized that KATP channels and Ca2+-activated potassium channels may exist in RER of the liver. Ion channel incorporation of RER of hepatocytes into the bilayer lipid membrane and western blotting allowed the identification of the rerKATP and Ca2+-activated potassium channels of intermediate conductance (rerIKCa channel). Single channel recordings revealed a 211 pS K channel، which was sensitive to 200 nM charibdotoxin. In addition، adding 2. 5 mM ATP، 100 μM glibenclamide and 400 μM tolbutamide inhibited a 596 pS potassium channel activity. According to the results of western blot analysis، Kir6. 2، SUR1 and/or SUR2B، SUR2A and IKCa were expressed in the endoplasmic reticulum fractions. The data obtained in this study demonstrate، in part، the composition of rerKATP channel and the presence of rerIKCa in the endoplasmic reticulum of the liver. These results will be useful for further analysis of the composition of rerKATP and rerIKCa channels and help to understand the role of these channels in diseases.

Intracellular pH (pHi) regulates essentially all aspects of cellular activities. However، it is unknown how endoplasmic reticulum (ER) potassium channels sense pHi. In this study، we investigate the direct effects of pHi on ER potassium channels. We used channel incorporation into the bilayer lipid membrane method. L-α-phosphatidylcholine، a membrane lipid، was extracted from fresh egg yolk. Bilayer lipid membrane was formed in a 150 μm diameter hole. Rough endoplasmic reticulum vesicles were obtained from the liver after homogenization and several centrifugations. All single channel recordings were filtered at 1 kHz and stored at a sampling rate of 10 kHz for offline analysis by PClamp10. The purity of cell fractions was confirmed by western blot using specific markers of mitochondria، plasma membrane، endoplasmic reticulum، and Golgi. The pH was measured with a pH meter (0. 001 unit accuracy). Statistical analysis was performed based on Markov noise free single channel analysis. Western blotting and antibodies directed against various cellular proteins revealed that ER fractions did not contain specific proteins of the other subcellular compartments. Single channel recordings revealed a 596 pS K+ channel، which was inhibited by 2. 5 mM ATP، 100 μM glibenclamide and 400 μM tolbutamide. No effect of increasing pHi to 8. 2 was found but decreasing pHi to below about 6. 7 produced a marked inhibition of channel activity، with complete block being observed at pHi 6. 2. Our results indicate that intracellular acidification inhibits ER K+ channel activities. The direct regulation of ER K+ channels by pHi has important implications for ER homeostasis.

Defects in endoplasmic reticulum homeostasis are common occurrences in different diseases، such as diabetes، in which the function of endoplasmic reticulum is disrupted. It is now well established that ion channels of endoplasmic reticulum membrane have a critical role in endoplasmic reticulum luminal homeostasis. Our previous studies showed the presence of an ATP-sensitive cationic channel in endoplasmic reticulum. Therefore، in this study، we examined and compared the activities of this channel in control and diabetic rats using single-channel recording techniques. Male Wistar rats were made diabetic for 2 weeks with a single dose injection of streptozotocin (45 mg/kg). Ion channel incorporation of rough endoplasmic reticulum of diabetic hepatocytes into the bilayer lipid membrane allowed the characterization of K+ channel. Ion channel incorporation of rough endoplasmic reticulum vesicles into the bilayer lipid revealed that the channel current-voltage (I-V) relation with a mean slope conductance of 520 ± 19 pS was unaffected in diabetes. Interestingly، the channel Po-voltage relation was significantly lower in diabetic rats at voltages above +30 mV. We concluded that the endoplasmic reticulum cationic channel is involved in diabetes. Also، this finding could be considered as a goal for further therapeutic plans.

Rough endoplasmic reticulum is important organelle that plays a role in the regulation of a range of functions. Potassium channels in the endoplasmic reticulum membrane were recently reported that its physiological role is unknown. Hepatocyte endoplasmic reticulum is a rich source of glucose 6- phosphatase that is involved in the control of gluconeogenesis. Since phosphate ions are intra-luminal metabolites for this enzyme of endoplasmic reticulum thus, in this study, the effect of phosphate ions on potassium channel activity was studied. Endoplasmic reticulum vesicles extraction was accomplished following liver excision in rats, homogenization and several stages of ultracentrifugation. Phosphatidylcholine was extracted from fresh egg yolk. Bilayer lipid membrane was formed in a 350 µm diameter aperture in between two chambers cis and trans contained 200/50 mMKCl solutions respectively, then vesicles were incorporated into bilayer lipid membrane. Ion channel activity was recorded by single channel recording technique both in control conditions and presence of phosphate ion in luminal face, next biophysical ion channel properties analyzed by Clampfit10 software. Endoplasmic reticulum Potassium channel was 550 pS conductance and its activity changed as voltage dependent manner in voltage range of +30 to -40 mV, in this respect the open probability and the average unitary current in a voltage + 30 mV were 0.73 and 26 pA, respectively. However, at lower voltages, the channel activity was minimal. In the presence of 50 mM phosphate ion, mean unitary current and also channel open probability did not change significantly in different voltages compared to the control condition (p>0.05). Rat hepatocyte endoplasmic reticulum membranes has been a kind of potassium channel with voltage-dependent activity and it seems that its electrophysiological characteristics did not influenced by phosphate anion in luminal face.