scholarly journals Inhibition of Cardiomyocytes Hypertrophy by Resveratrol Is Associated with Amelioration of Endoplasmic Reticulum Stress

2016 ◽  
Vol 39 (2) ◽  
pp. 780-789 ◽  
Author(s):  
Yan Lin ◽  
Jingbin Zhu ◽  
Xiaojie Zhang ◽  
Jun Wang ◽  
Wei Xiao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Protein Expression ◽  
Er Stress ◽  
Surface Area ◽  
Myocardial Cell ◽  
Control Group ◽  
Cell Surface Area ◽  
Transmission Electron

Background/Aims: Resveratrol (Res), a polyphenol antioxidant found in red wine, has been shown to play a cardioprotective role. This study was undertaken to investigate whether Res can protect the heart suffering from hypertrophy injuries induced by isoproterenol (ISO), and whether the protective effect is mediated by endoplasmic reticulum (ER) stress. Methods: Cardiomyocytes were randomly assigned to the control group, ISO group (100 nM ISO for 48 h), Res + ISO group (50 μM Res and 100 nM ISO for 48 h) and Res group (50 μM Res for 48h only). Hypertrophy was estimated by measuring the cell surface area and the atrial natriuretic peptide (ANP) gene expression. Apoptosis was measured using Hoechst 33258 staining and transmission electron microscopy. Protein expression of ER stress and apoptosis factors was analyzed using Western Blot analysis. Results: Res effectively suppress the cardiomyocytes hypertrophy and apoptosis induced by ISO, characterized by the reduction of the myocardial cell surface area, the ANP gene expression, the LDH and MDA leakage amount and the rate of cell apoptosis, while decrease of the protein expression of GRP78, GRP94 and CHOP, and reverse the expression of Bcl-2 and Bax. Conclusion: In summary, Res treatment effectively suppressed myocardial hypertrophy and apoptosis at least partially via inhibiting ER stress.

scholarly journals MiR-26a-5p inhibits GSK3β expression and promotes cardiac hypertrophy in vitro

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10371
Author(s):  
Liqun Tang ◽  
Jianhong Xie ◽  
Xiaoqin Yu ◽  
Yangyang Zheng
Keyword(s):  
Cell Surface ◽  
Cardiac Hypertrophy ◽  
Surface Area ◽  
Myocardial Cell ◽  
Immunofluorescence Staining ◽  
Cell Surface Area ◽  
Direct Target

Background The role of miR-26a-5p expression in cardiac hypertrophy remains unclear. Herein, the effect of miR-26a-5p on cardiac hypertrophy was investigated using phenylephrine (PE)-induced cardiac hypertrophy in vitro and in a rat model of hypertension-induced hypertrophy in vivo. Methods The PE-induced cardiac hypertrophy models in vitro and vivo were established. To investigate the effect of miR-26a-5p activation on autophagy, the protein expression of autophagosome marker (LC3) and p62 was detected by western blot analysis. To explore the effect of miR-26a-5p activation on cardiac hypertrophy, the relative mRNA expression of cardiac hypertrophy related mark GSK3β was detected by qRT-PCR in vitro and vivo. In addition, immunofluorescence staining was used to detect cardiac hypertrophy related mark α-actinin. The cell surface area was measured by immunofluorescence staining. The direct target relationship between miR-26a-5p and GSK3β was confirmed by dual luciferase report. Results MiR-26a-5p was highly expressed in PE-induced cardiac hypertrophy. MiR-26a-5p promoted LC3II and decreased p62 expression in PE-induced cardiac hypertrophy in the presence or absence of lysosomal inhibitor. Furthermore, miR-26a-5p significantly inhibited GSK3β expression in vitro and in vivo. Dual luciferase report results confirmed that miR-26a-5p could directly target GSK3β. GSK3β overexpression significantly reversed the expression of cardiac hypertrophy-related markers including ANP, ACTA1 and MYH7. Immunofluorescence staining results demonstrated that miR-26a-5p promoted cardiac hypertrophy related protein α-actinin expression, and increased cell surface area in vitro and in vivo. Conclusion Our study revealed that miR-26a-5p promotes myocardial cell autophagy activation and cardiac hypertrophy by regulating GSK3β, which needs further research.

scholarly journals Differential regulation of tropomyosin isoform organization and gene expression in response to altered actin gene expression.

1993 ◽  
Vol 121 (4) ◽  
pp. 811-821 ◽  
Author(s):  
G Schevzov ◽  
C Lloyd ◽  
D Hailstones ◽  
P Gunning
Keyword(s):  
Gene Expression ◽  
Cell Surface ◽  
Surface Area ◽  
Stress Fiber ◽  
Actin Gene ◽  
Cell Surface Area ◽  
Protein Levels ◽  
Differential Pattern ◽  
Myoblast Cells ◽  
Twofold Decrease

Phenotypically altered C2 myoblast cells, generated by the stable transfection of human nonmuscle actin genes (Schevzov, G., C. Lloyd, and P. Gunning. 1992. J. Cell Biol. 117:775-786), exhibit a differential pattern of tropomyosin cellular organization and isoform gene expression. The beta-actin transfectants displaying a threefold increase in the cell surface area, showed no significant changes in the pattern of organization of the high M(r) tropomyosin isoform, Tm 2, or the low M(r) tropomyosin isoform, Tm 5. In contrast, the gamma- and beta sm-actin gene transfectants, exhibiting a twofold decrease in the cell surface area, had an altered organization of Tm 2 but not Tm 5. In these actin transfectants, Tm 2 did not preferentially segregate into stress fiber-like structures and the intensity of staining was greatly diminished. Conversely, a well-defined stress fiber-like organization of Tm 5 was observed. The pattern of organization of these tropomyosin isoforms correlated with their expression such that a profound decrease in Tm 2 expression was observed both at the transcript and protein levels, whereas Tm 5 remained relatively unchanged. These results suggest that relative changes in nonmuscle actin gene expression can affect the organization and expression of tropomyosin in an isoform specific manner. Furthermore, this apparent direct link observed between actin and tropomyosin expression suggests that nonpharmacological signals originating in the cytoskeleton can regulate cytoarchitectural gene expression.

scholarly journals The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes

2019 ◽  
Vol 8 (9) ◽  
pp. 1322 ◽  
Author(s):  
Irene Escribano-López ◽  
Aranzazu M de Marañon ◽  
Francesca Iannantuoni ◽  
Sandra López-Domènech ◽  
Zaida Abad-Jiménez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Protein Expression ◽  
Er Stress ◽  
Leukocyte Adhesion ◽  
Calcium Content ◽  
Rolling Velocity

Mitochondrial dysfunction has been shown to play a central role in the pathophysiology of type 2 diabetes (T2D), and mitochondria-targeted agents such as SS-31 are emerging as a promising strategy for its treatment. We aimed to study the effects of SS-31 on leukocytes from T2D patients by evaluating oxidative stress, endoplasmic reticulum (ER) stress and autophagy. Sixty-one T2D patients and 53 controls were included. Anthropometric and analytical measurements were performed. We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31. Furthermore, we have evaluated the action of SS-31 on leukocyte-endothelium interactions. T2D patients exhibited elevated ROS concentration, calcium levels and presence of ER markers (GRP78 and CHOP gene expression, and GRP78 and P-eIF2α protein expression), all of which were reduced by SS-31 treatment. SS-31 also led to a drop in BECN1 gene expression, and Beclin1 and LC3 II/I protein expression in T2D patients. In contrast, the T2D group displayed reduced p62 protein levels that were restored by SS-31. SS-20 (with non-antioxidant activity) did not change any analyzed parameter. In addition, SS-31 decreased rolling flux and leukocyte adhesion, and increased rolling velocity in T2D patients. Our findings suggest that SS-31 exerts potentially beneficial effects on leukocytes of T2D patients modulating oxidative stress and autophagy, and ameliorating ER stress.

Differential AMPK phosphorylation sites associated with phenylephrine vs. antihypertrophic effects of adenosine agonists in neonatal rat ventricular myocytes

2010 ◽  
Vol 298 (5) ◽  
pp. H1382-H1390 ◽  
Author(s):  
Theresa Pang ◽  
Venkatesh Rajapurohitam ◽  
Michael A. Cook ◽  
Morris Karmazyn
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Cell Surface ◽  
Surface Area ◽  
Adenosine Receptor ◽  
Neonatal Rat ◽  
Adenosine Receptor Agonists ◽  
Cell Surface Area ◽  
Receptor Agonists ◽  
Ampk Phosphorylation

Stimulation of cardiac AMP-activated protein kinase (AMPK) has been demonstrated in both prohypertrophic and antihypertrophic settings, although the reasons for such discrepant results are not well understood. We determined how AMPK is regulated in response to phenylephrine-induced cardiomyocyte hypertrophy and assessed whether AMPK activity may be a factor underlying the antihypertrophic effect of adenosine receptor agonists. The role of AMPK in hypertrophic responses was determined by assessing the effect of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside on three hypertrophic indexes, including protein synthesis, cell surface area, and fetal gene expression. The changes in phosphorylation of the catalytic α-subunit of AMPK at two different sites, Thr172 and Ser485/491, in response to phenylephrine and adenosine receptor agonists were also examined. 5-Aminoimidazole-4-carboxyamide ribonucleoside completely abolished phenylephrine-induced increases in protein synthesis, cell surface area, and fetal gene expression. AMPK phosphorylation time course studies revealed that phenylephrine induced a time-dependent activation at site Ser485/491, in contrast to adenosine receptor agonists, which demonstrated rapid AMPK phosphorylation at Thr172. Furthermore, the phosphorylation at Ser485/491 by phenylephrine was not affected by the addition of adenosine receptor agonists, although, conversely, phosphorylation of AMPK at Thr172 by adenosine receptor agonists was abrogated by the addition of phenylephrine. We propose from these results that cardiomyocyte hypertrophic and antihypertrophic responses, at least with respect to inhibition of phenylephrine-induced hypertrophy by adenosine receptor agonists, are mediated by multisite AMPK regulation. The latter are reflected by increased phosphorylation at Ser485/491 and at Thr172, associated with prohypertrophic and antihypertrophic responses, respectively.

scholarly journals Elevation of gene expression of Btg2, Gadd 153, and antioxidant markers in RONS-induced PC12 cells

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Aravind P ◽  
Sarojini R. Bulbule ◽  
Hemalatha N ◽  
Anushree G ◽  
Babu R.L ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endoplasmic Reticulum ◽  
Protein Expression ◽  
Pc12 Cells ◽  
Expression Pattern ◽  
High Glucose ◽  
Nitrosative Stress ◽  
Gene Expression Pattern ◽  
Marker Genes ◽  
Differential Stress

Abstract Background Free radicals generated in the biological system bring about modifications in biological molecules causing damage to their structure and function. Identifying the damage caused by ROS and RNS is important to predict the pathway of apoptosis due to stress in PC12 cells. The first defense mechanisms against them are antioxidants which act in various pathways through important cellular organelles like the mitochondria and endoplasmic reticulum. Specific biomarkers like Gadd153 which is a marker for endoplasmic reticulum stress, Nrf2 which responds to the redox changes and translocates the antioxidant response elements, and Btg2 which is an antioxidant regulator have not been addressed in different stress conditions previously in PC12 cells. Therefore, the study was conducted to analyze the gene expression pattern (SOD, Catalase, Btg2, Gadd153, and Nrf2) and the protein expression pattern (iNOS and MnSOD) of the antioxidant stress markers in differential stress-induced PC12 cells. Peroxynitrite (1 μM), rotenone (1 μM), H2O2(100 mM), and high glucose (33 mM) were used to induce oxidative and nitrosative stress in PC12 cells. Results The results obtained suggested that rotenone-induced PC12 cells showed a significant increase in the expression of catalase, Btg2, and Gadd153 compared to the control. Peroxynitrite-induced PC12 cells showed higher expression of Btg2 compared to the control. H2O2 and high glucose showed lesser expression compared to the control in all stress marker genes. In contrast, the Nrf2 gene expression is downregulated in all the stress-induced PC12 cells compared to the control. Further, MnSOD and iNOS protein expression studies suggest that PC12 cells exhibit a selective downregulation. Lower protein expression of MnSOD and iNOS may be resulted due to the mitochondrial dysfunction in peroxynitrite-, high glucose-, and H2O2-treated cells, whereas rotenone-induced cells showed lower expression, which could be the result of a dysfunction of the endoplasmic reticulum. Conclusion Different stress inducers like rotenone, peroxynitrite, H2O2, and high glucose increase the NO and ROS. Btg2 and Gadd153 genes were upregulated in the stress-induced cells, whereas the Nrf2 was significantly downregulated in differential stress-induced PC12 cells. Further, antioxidant marker genes were differentially expressed with different stress inducers.

scholarly journals IreA controls endoplasmic reticulum stress-induced autophagy and survival through homeostasis recovery

2018 ◽  
pp. MCB.00054-18 ◽  
Author(s):  
Eunice Domínguez-Martín ◽  
Laura Ongay-Larios ◽  
Laura Kawasaki ◽  
Olivier Vincent ◽  
Gerardo Coello ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Survival ◽  
Eukaryotic Cell ◽  
Functional Link ◽  
Unfolded Protein ◽  
Transcriptional Changes ◽  
The Unfolded Protein Response ◽  
Protein Response

The Unfolded Protein Response (UPR) is an adaptive pathway that restores cellular homeostasis after endoplasmic reticulum (ER) stress. The ER-resident kinase/ribonuclease Ire1 is the only UPR sensor conserved during evolution. Autophagy, a lysosomal degradative pathway, also contributes to the recovery of cell homeostasis after ER-stress but the interplay between these two pathways is still poorly understood. We describe the Dictyostelium discoideum ER-stress response and characterize its single bonafide Ire1 orthologue, IreA. We found that tunicamycin (TN) triggers a gene-expression reprogramming that increases the protein folding capacity of the ER and alleviates ER protein load. Further, IreA is required for cell-survival after TN-induced ER-stress and is responsible for nearly 40% of the transcriptional changes induced by TN. The response of Dictyostelium cells to ER-stress involves the combined activation of an IreA-dependent gene expression program and the autophagy pathway. These two pathways are independently activated in response to ER-stress but, interestingly, autophagy requires IreA at a later stage for proper autophagosome formation. We propose that unresolved ER-stress in cells lacking IreA causes structural alterations of the ER, leading to a late-stage blockade of autophagy clearance. This unexpected functional link may critically affect eukaryotic cell survival under ER-stress.

scholarly journals Ca2+-activated cleavage of ezrin visualised dynamically in living myeloid cells during cell surface area expansion

2020 ◽  
Vol 133 (5) ◽  
pp. jcs236968 ◽  
Author(s):  
Rhiannon E. Roberts ◽  
Marianne Martin ◽  
Sabrina Marion ◽  
Geetha L. Elumalai ◽  
Kimberly Lewis ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Area ◽  
Myeloid Cells ◽  
Cell Surface Area ◽  
Area Expansion
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