Assignment&lt;footref rid="foot01"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/footref&gt; of the yeast APG5 human homologue APG5L to chromosome band 6q21 by fluorescence in situ hybridisation

Schmeiser, Kurt; Armstrong, Susan J.; Hammond, Ester M.; Grand, Roger J. A.

doi:10.1159/000015471

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…The conjugation of the activated Apg12p to Apg5p is performed by Apg10p, a ubiquitin E2-like conjugation enzyme (60). The human homologues for Apg10p and Apg5p have been identified (55). Thus, this conjugation process appears to be conserved throughout eukaryotes, including humans (41,42).…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Traffics to Autophagosomes in Human Coronary Artery Endothelial Cells

Dorn¹,

2001

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Porphyromonas gingivalis is a periodontal pathogen that also localizes to atherosclerotic plaques. Our previous studies demonstrated that P. gingivalis is capable of invading endothelial cells and that intracellular bacteria are contained in vacuoles that resemble autophagosomes. In this study, we have examined the trafficking of P. gingivalis 381 to the autophagic pathway. P. gingivalis 381 internalized by human coronary artery endothelial (HCAE) cells is located within vacuoles morphologically identical to autophagosomes. The progression of P. gingivalis 381 through intracellular vacuoles was analyzed by immunofluorescence microscopy. Vacuoles containing P. gingivalis colocalize with Rab5 and HsGsa7p early after internalization. At later times, P. gingivalis colocalizes with BiP and then progresses to a vacuole that contains BiP and lysosomal glycoprotein 120. Late endosomal markers and the lysosomal cathepsin L do not colocalize with P. gingivalis 381. The intracellular survival of P. gingivalis 381 decreases over 8 h in HCAE cells pretreated with the autophagy inhibitors 3-methyladenine and wortmannin. In addition, the vacuole containing P. gingivalis 381 lacks BiP but contains cathepsin L in the presence of wortmannin. These results suggest that P. gingivalis 381 evades the endocytic pathway to lysosomes and instead traffics to the autophagosome.Porphyromonas gingivalis is a gram-negative, anaerobic rod that is considered to be among the major pathogens associated with adult periodontitis (64). A possible mechanism of pathogenesis may be cellular invasion. P. gingivalis has been demonstrated to be internalized within gingival epithelial cells in vitro (19,34,53) and buccal epithelial cells in vivo (51). Recent epidemiological studies have demonstrated a strong relationship between periodontal disease and coronary heart disease (2,3,17,38,39). Oral bacteria have a direct route to the circulatory system in periodontitis patients due to transient bacteremias produced by flossing, mastication, and toothbrushing (11,57,62). P. gingivalis localizes to atherosclerotic plaques (12,30) and is capable of invasion of coronary artery cells in vitro (16,18). Therefore, invasion and intracellular parasitism of endothelial cells by P. gingivalis in vivo may exacerbate the inflammatory response of atherosclerosis.Invasion of nonphagocytic cells is a common strategy of evading the immune system for many pathogens (23). Once within the cell, these pathogens have developed various mechanisms for survival (28,40). Legionella pneumophila and virulent Brucella abortus gain access to and replicate in vacuoles that resemble autophagosomes and are associated with endoplasmic reticulum proteins (46, 47). Autophagosomes, multimembranous vacuoles formed from invaginations of ribosome-free regions of the rough endoplasmic reticulum (RER) (20), are the organelles of the autophagic process. Autophagy is a process whereby cytosol and organelles are sequestered for lysosome degradation in response to nutrient deprivation (20). Under normal...

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Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Traffics to Autophagosomes in Human Coronary Artery Endothelial Cells

Dorn¹,

2001

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“…erefore, the genetic variant in the ATG5 gene promoter may affect its transcription activity and change ATG5 levels, contributing to the AMI development as a rare risk factor. e human ATG5 gene has been mapped to 6q21 [31]. It is transcribed into the mRNAs of 3.3 kb, 2.5 kb, and 1.8 kb at comparable levels in viable cells [32].…”

Section: Discussionmentioning

confidence: 99%

Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction

Zhang

et al. 2020

Cardiology Research and Practice

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Coronary artery disease (CAD) including acute myocardial infarction (AMI) is an inflammatory and metabolic disease mainly caused by atherosclerosis. Dysfunctional autophagy has been associated with abnormal lipid metabolism and inflammation. In previous studies, we have reported altered autophagic activity in AMI patients. As autophagy-related protein 5 (ATG5) is a core protein in autophagy, we speculated that altered ATG5 level may contribute to CAD and AMI development. In this study, the promoter of the ATG5 gene was genetically and functionally investigated in large groups of AMI patients (n = 378) and ethnic-matched healthy controls (n = 386). The results showed that a total of 15 genetic variants including 6 single-nucleotide polymorphisms (SNPs) in the ATG5 gene promoter were found in this study population. A novel deletion variant (g.106326168_70delTCT) and an SNP [g.106325757C > G (rs190825454)] were found in one 66-year-old male patient with non-ST-segment elevated AMI, but in none of controls. In cultured HEK-293 and H9c2 cells, the deletion variant significantly decreased the transcriptional activity of the ATG5 gene promoter (P<0.01). In contrast, the genetic variants either identified only in controls or found in both AMI patients and controls did not affect the transcriptional activity of the ATG5 gene promoter (P>0.05). Furthermore, an electrophoretic mobility shift assay showed that the deletion variant evidently affected the binding of a transcription factor. Therefore, the genetic variant identified in AMI may affect the activity of the ATG5 gene promoter and change the ATG5 level, contributing to AMI as a rare risk factor.

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A novel and functional variant within the ATG5 gene promoter in sporadic Parkinson's disease

Chen

Zhu

Wang

et al. 2013

Neuroscience Letters

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Assignment<footref rid="foot01"><sup>1</sup></footref> of the yeast APG5 human homologue APG5L to chromosome band 6q21 by fluorescence in situ hybridisation

Cited by 3 publications

References 6 publications

Porphyromonas gingivalis Traffics to Autophagosomes in Human Coronary Artery Endothelial Cells

Porphyromonas gingivalis Traffics to Autophagosomes in Human Coronary Artery Endothelial Cells

Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction

A novel and functional variant within the ATG5 gene promoter in sporadic Parkinson's disease

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