scholarly journals Genes Encoding ACE2, TMPRSS2 and Related Proteins Mediating SARS-CoV-2 Viral Entry are Upregulated with Age in Human Cardiomyocytes

2020 ◽  
Author(s):  
Emma L. Robinson ◽  
Kanar Alkass ◽  
Olaf Bergmann ◽  
Janet J. Maguire ◽  
H. Llewelyn Roderick ◽  
...  
Keyword(s):  
Viral Entry ◽  
Enzyme Inhibitors ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Older Individuals ◽  
Human Cardiomyocytes ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Approved Drugs ◽  
Related Proteins

AbstractAge is an independent risk factor for adverse outcome in patients following COVID-19 infection. We hypothesised that differential expression of genes encoding proteins proposed to be required for entry of SARS-Cov-2 in aged compared to younger cardiomyocytes might contribute to the susceptibility of older individuals to COVID-19-associated cardiovascular complications.We generated strand-specific RNA-sequencing libraries from RNA isolated from flow-sorted cardiomyocyte nuclei from left ventricular tissue. RNASeq data were compared between five young (19-25yr) and five older (63-78yr) Caucasian males who had not been on medication or exhibited evidence of cardiovascular disease post-mortem.Expression of relevant genes encoding ACE2, TMPRSS2, TMPRS11D, TMPRS11E, FURIN, CTSL, CTSB and B0AT1/SLC6A19 were upregulated in aged cardiomyocytes and the combined relative cardiomyocyte expression of these genes correlated positively with age. Genes encoding proteins in the RAAS and interferon/interleukin pathways were also upregulated such as ACE, AGTR1, MAS1 and IL6R.Our results highlight SARS-CoV-2 related genes that have higher expression in aged compared with young adult cardiomyocytes. These data may inform studies using selective enzyme inhibitors/antagonists, available as experimental compounds or clinically approved drugs e.g. remdesivir that has recently been rapidly accepted for compassionate use, to further understand the contribution of these pathways in human cardiomyocytes to disease outcome in COVID-19 patients.

scholarly journals Genes encoding ACE2, TMPRSS2 and related proteins mediating SARS-CoV-2 viral entry are upregulated with age in human cardiomyocytes

2020 ◽  
Vol 147 ◽  
pp. 88-91 ◽  
Author(s):  
Emma L. Robinson ◽  
Kanar Alkass ◽  
Olaf Bergmann ◽  
Janet J. Maguire ◽  
H. Llewelyn Roderick ◽  
...  
Keyword(s):  
Viral Entry ◽  
Human Cardiomyocytes ◽  
Genes Encoding ◽  
Related Proteins

scholarly journals Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease

2007 ◽  
Vol 28 (3) ◽  
pp. 284-293 ◽  
Author(s):  
Sarah Glyn-Jones ◽  
Sarah Song ◽  
Michael A. Black ◽  
Anthony R. J. Phillips ◽  
Soon Y. Choong ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Molecular Basis ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Myocardial Disease ◽  
Chronic Hyperglycemia ◽  
Expression Of Genes ◽  
Streptozotocin Induced Diabetes ◽  
Quantitative Verification ◽  
Disproportionate Number

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diastolic dysfunction and heart failure in diabetes, but its molecular basis has remained obscure, in part because of its multifactorial origins. Here we employed comparative transcriptomic methods with quantitative verification of selected transcripts by reverse transcriptase quantitative PCR to characterize the molecular basis of DCM in rats with streptozotocin-induced diabetes of 16-wk duration. Diabetes caused left ventricular disease that was accompanied by significant changes in the expression of 1,614 genes, 749 of which had functions assignable by Gene Ontology classification. Genes corresponding to proteins expressed in mitochondria accounted for a disproportionate number of those whose expression was significantly modified in DCM, consistent with the idea that the mitochondrion is a key target of the pathogenic processes that cause myocardial disease in diabetes. Diabetes also induced global perturbations in the expression of genes regulating cardiac fatty acid metabolism, whose dysfunction is likely to play a key role in the promotion of oxidative stress, thereby contributing to the pathogenesis of diabetic myocardial disease. In particular, these data point to impaired regulation of mitochondrial β-oxidation as central in the mechanisms that generate DCM pathogenesis. This study provides a comprehensive molecular snapshot of the processes leading to myocardial disease in diabetes.

scholarly journals GABA Accumulation Causes Cell Elongation Defects and a Decrease in Expression of Genes Encoding Secreted and Cell Wall-Related Proteins in Arabidopsis thaliana

2011 ◽  
Vol 52 (5) ◽  
pp. 894-908 ◽  
Author(s):  
Hugues Renault ◽  
Abdelhak El Amrani ◽  
Ravishankar Palanivelu ◽  
Emily P. Updegraff ◽  
Agnès Yu ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Cell Wall ◽  
Cell Elongation ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Gaba Accumulation ◽  
Related Proteins

scholarly journals Coordination of plastid and nuclear gene expression

2003 ◽  
Vol 358 (1429) ◽  
pp. 135-145 ◽  
Author(s):  
John C. Gray ◽  
James A. Sullivan ◽  
Jun-Hui Wang ◽  
Cheryl A. Jerome ◽  
Daniel MacLean
Keyword(s):  
Nuclear Gene ◽  
Nuclear Genes ◽  
Regulation Of Transcription ◽  
Nuclear Gene Expression ◽  
Plastid Genomes ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Coordinated Expression ◽  
Plastid Protein ◽  
Related Proteins

The coordinated expression of genes distributed between the nuclear and plastid genomes is essential for the assembly of functional chloroplasts. Although the nucleus has a pre–eminent role in controlling chloroplast biogenesis, there is considerable evidence that the expression of nuclear genes encoding photosynthesis–related proteins is regulated by signals from plastids. Perturbation of several plastid–located processes, by inhibitors or in mutants, leads to decreased transcription of a set of nuclear photosynthesis–related genes. Characterization of arabidopsis gun ( genomes uncoupled ) mutants, which express nuclear genes in the presence of norflurazon or lincomycin, has provided evidence for two separate signalling pathways, one involving tetrapyrrole biosynthesis intermediates and the other requiring plastid protein synthesis. In addition, perturbation of photosynthetic electron transfer produces at least two different redox signals, as part of the acclimation to altered light conditions. The recognition of multiple plastid signals requires a reconsideration of the mechanisms of regulation of transcription of nuclear genes encoding photosynthesis–related proteins.

Expression of genes encoding PR10 class pathogenesis-related proteins is inhibited in yellow lupine root nodules

Plant Science ◽  
1999 ◽  
Vol 149 (2) ◽  
pp. 125-137 ◽  
Author(s):  
Michał M Sikorski ◽  
Jacek Biesiadka ◽  
Alina E Kasperska ◽  
Joanna Kopcińska ◽  
Barbara Łotocka ◽  
...  
Keyword(s):  
Root Nodules ◽  
Pathogenesis Related Proteins ◽  
Expression Of Genes ◽  
Pathogenesis Related ◽  
Genes Encoding ◽  
Yellow Lupine ◽  
Related Proteins

scholarly journals Insulin receptor substrate 1 gene expression is strongly up-regulated by HSPB8 silencing in U87 glioma cells

2020 ◽  
Vol 54 (4) ◽  
pp. 231-243
Author(s):  
Oksana S. Hnatiuk ◽  
Dariia O. Tsymbal ◽  
Dmytro O. Minchenko ◽  
Olena O. Khita ◽  
Yulia M. Viletska ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Quantitative Polymerase Chain Reaction ◽  
Glioma Cells ◽  
Insulin Receptor Substrate ◽  
Gene Expressions ◽  
Insulin Receptor Substrate 1 ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
The Stability ◽  
Related Proteins

Abstract Objective. The aim of the present investigation was to study the expression of genes encoding IRS1 (insulin receptor substrate 1) and some other functionally active proteins in U87 glioma cells under silencing of polyfunctional chaperone HSPB8 for evaluation of the possible significance of this protein in intergenic interactions. Methods. Silencing of HSPB8 mRNA was introduced by HSPB8 specific siRNA. The expression level of HSPB8, IRS1, HK2, GLO1, HOMER3, MYL9, NAMPT, PER2, PERP, GADD45A, and DEK genes was studied in U87 glioma cells by quantitative polymerase chain reaction. Results. It was shown that silencing of HSPB8 mRNA by specific to HSPB8 siRNA led to a strong down-regulation of this mRNA and significant modification of the expression of IRS1 and many other genes in glioma cells: strong up-regulated of HOMER3, GLO1, and PERP and down-regulated of MYL9, NAMPT, PER2, GADD45A, and DEK gene expressions. At the same time, no significant changes were detected in the expression of HK2 gene in glioma cells treated by siRNA, specific to HSPB8. Moreover, the silencing of HSPB8 mRNA enhanced the glioma cells proliferation rate. Conclusions. Results of this investigation demonstrated that silencing of HSPB8 mRNA affected the expression of IRS1 gene as well as many other genes encoding tumor growth related proteins. It is possible that the dysregulation of most of the studied genes in glioma cells after silencing of HSPB8 is reflected by a complex of intergenic interactions and that this polyfunctional chaperone is an important factor for the stability of genome function and regulatory mechanisms contributing to the tumorigenesis control.

scholarly journals LAMP2 Cardiomyopathy: Consequences of Impaired Autophagy in the Heart

2021 ◽  
Author(s):  
Ronny Alcalai ◽  
Michael Arad ◽  
Hiroko Wakimoto ◽  
Dor Yadin ◽  
Joshua Gorham ◽  
...  
Keyword(s):  
Cardiac Electrophysiology ◽  
Morphological Changes ◽  
Systolic Function ◽  
Left Ventricular ◽  
Danon Disease ◽  
Conduction Disturbances ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Increased Sensitivity ◽  
Protein Components

Background Human mutations in the X‐linked lysosome‐associated membrane protein‐2 ( LAMP2 ) gene can cause a multisystem Danon disease or a primary cardiomyopathy characterized by massive hypertrophy, conduction system abnormalities, and malignant ventricular arrhythmias. We introduced an in‐frame LAMP2 gene exon 6 deletion mutation (denoted L2 Δ6 ) causing human cardiomyopathy, into mouse LAMP2 gene, to elucidate its consequences on cardiomyocyte biology. This mutation results in in‐frame deletion of 41 amino acids, compatible with presence of some defective LAMP2 protein. Methods and Results Left ventricular tissues from L2 Δ6 and wild‐type mice had equivalent amounts of LAMP2 RNA, but a significantly lower level of LAMP2 protein. By 20 weeks of age male mutant mice developed left ventricular hypertrophy which was followed by left ventricular dilatation and reduced systolic function. Cardiac electrophysiology and isolated cardiomyocyte studies demonstrated ventricular arrhythmia, conduction disturbances, abnormal calcium transients and increased sensitivity to catecholamines. Myocardial fibrosis was strikingly increased in 40‐week‐old L2 Δ6 mice, recapitulating findings of human LAMP2 cardiomyopathy. Immunofluorescence and transmission electron microscopy identified mislocalization of lysosomes and accumulation of autophagosomes between sarcomeres, causing profound morphological changes disrupting the cellular ultrastructure. Transcription profile and protein expression analyses of L2 Δ6 hearts showed significantly increased expression of genes encoding activators and protein components of autophagy, hypertrophy, and apoptosis. Conclusions We suggest that impaired autophagy results in cardiac hypertrophy and profound transcriptional reactions that impacted metabolism, calcium homeostasis, and cell survival. These responses define the molecular pathways that underlie the pathology and aberrant electrophysiology in cardiomyopathy of Danon disease.

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