Aging is associated with hypermethylation of autophagy genes in macrophages

Khalil, Hany; Tazi, Mia; Caution, Kyle; Ahmed, Amr E.; Kanneganti, Apurva; Assani, Kaivon; Kopp, Benjamin T.; Marsh, Clay B.; Dakhlallah, Duaa; Amer, Amal O.

doi:10.1080/15592294.2016.1144007

Cited by 107 publications

(92 citation statements)

References 34 publications

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“…Interestingly, the mutant genotype TT of IL-4 occurred in C-589T promoter locus in which the nucleotides CC have been modified to TT. This modification in C to T nucleotide indicates the possible involvement of DNA methylation and epigenetic modification of IL-4 promoter sequences and, subsequently, disturbance of IL-4 expression in HCVinfected patients [24,36]. Our results indicate that high level of HCV load of viremia leads to high secretion of IL-6, which regulates interferon regulatory factor 1(IRF1) and inhibits cell growth, leading to stimulation of necrosis factors and cell death [7,37].…”

Section: Discussionmentioning

confidence: 75%

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Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt

Khalil

Arfa

El-Masrey

et al. 2017

J Infect Dev Ctries

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Introduction: Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). It can cause both acute and chronic hepatitis infection. Based on secretion of required cytokines upon infection, HCV can improve its own RNA and successfully complete the replication cycle. Importantly, single nucleotide polymorphisms (SNPs) are the most common type of genetic variation and have been found to play a critical role in modulation of cellular cytokine production and interaction. Methodology: A total of 100 blood samples were obtained from HCV patients, and 120 samples were obtained from healthy individuals who served as controls. SNPs of interleukin-10/592 (IL-10/592) and IL-4/589 were investigated for possible connection with HCV infection. Relative expression of IL-4, IL-6, and IL-10 were detected using real-time polymerase chain reaction and enzyme-linked immunosorbent assay Results: The polymorphisms of IL-10 revealed a high rate of mutant genotype CC within the location IL-10/592 in HCV patients and controls, which resulted in low secretion of IL-10. Interestingly, the findings here demonstrate a positive association between HCV load of viremia and the mutant genotype IL-4-589/TT accompanied with low expression IL-4 in comparison with IL-6 expression. Conclusions: These data suggest that the expression of IL-4 is inversely proportional to HCV load of viremia, and this connection is due to the high level of mutant genotype IL-4-589/TT in infected patients located in gene promoter and inhibits gene expression.

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Section: Discussionmentioning

confidence: 75%

“…(∆∆Ct) = ∆Ct -∆Ct-normalized control. Lastly, the relative gene expression is equal 2 -ΔΔct of the final values [23,24].…”

Section: Discussionmentioning

confidence: 99%

Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt

Khalil

Arfa

El-Masrey

et al. 2017

J Infect Dev Ctries

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“…EpiTect Methyl II DNA Restriction Kit (Qiagen) was used to digest autophagy genes based on the methylation sensitive and dependent restriction sites. Fold changes of methylated molecules was calculated according the manufacture protocol [6].…”

Section: Detection Of Methylation Activitymentioning

confidence: 99%

“…Methylation of CpG islands promoter suppresses the expression of corresponding genes due to poor recognition by transcription factors [4,5]. Consequently, the DNA methylation pattern modifies a certain protein expression profile which is ultimately associated with various human aging disorders such as Alzheimer's (AD), and carcinogenicity [6]. Autophagy processes is characterized by accumulation of double-membraned cytoplasmic vacuoles regulating degradation events and recycling of cellular contents by delivering cytoplasmic materials, required for degradation, to lysosomes.…”

Section: Introductionmentioning

confidence: 99%

Epigenetics Reprogramming of Autophagy is involved in Childhood Acute Lymphatic Leukemi

Hassen¹,

Bassiouny²,

El-Shenawy³

et al. 2017

Pediatric Infect Dis

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Cancer disease has been considered as a result of progressive genetic alterations such as mutations in tumor suppressor genes and oncogenes, chromosomal abnormality and epigenetics reprogramming. Epigenetic modification plays a crucial role in the tumor initiation and tumor evaluation via DNA methylation activity and chromatin alternation mechanism. Noteworthy, autophagy is a fundamental, conserved physiological process by which cells target long-lived cytosolic proteins and organelles for lysosomal degradation. Recently, autophagy has been showed to play critical role in cancer evaluation and therapeutical strategy. On the other hand, lymphatic leukaemia is a type of cancer which contains two major conditions, acute and chronic leukaemia. Acute lymphatic leukemia (ALL) is the most common cancer in the pediatric population. Therefore, in the current work we were interested to investigate the possible involvement of DNA methylation of cellular genes in blood samples that derived from children with ALL. Interestingly, the relative expression of DNA methyltransferase 1 (DNMT1) has been increased in ALL samples compared to healthy individual samples. Meanwhile, the relative expression of cellular autophagy genes (LC3B and Atg5) has been strongly decreased in ALL samples suggesting the possible involvement of DNA methylation of related autophagy molecules. Accordingly, digestion of LC3B gene segment with restriction enzyme (HpaII) that specifically targeted CpG position showed inactive digestion on ALL samples in comparison with control samples indicating the possible methyl alternation of cytosine nucleotides. Further, we found another methylation activity on promoter regions of Atg5 and LC3B in ALL derived samples. These data strongly suggest that the expression of cellular autophagy genes LC3B and Atg5 are reduced and subsequently autophagic machinery is interrupted in ALL cases most likely via DNA methylation activity.

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“…The autophagy processes is characterized by accumulation of double-membrane cytoplasmic vacuoles regulating degradation events and recycling of cellular contents by delivering cytoplasmic materials, required for degradation, to lysosomes. Moreover, autophagy has been shown to play an important role in cell growth, development, aging and disease pathology [12,13]. The activation of PI3K and its downstream effector Akt/protein kinase have been identified at early stage upon influenza infection.…”

Section: Introductionmentioning

confidence: 99%

The Intracellular Signalling that Associated with Influenza A Virus Infection

Khalil¹

2017

Pediatric Infect Dis

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Influenza-A virus infection induces a variety of intracellular signalling pathways that are either antiviral or required to ensure efficient replication. A prominent cellular antiviral event is the activation of cascade that produces type I interferon's (IFNs): IFN-α and IFN-β. Consequently, an appreciated number of antiviral proteins that encoded by so-called IFN stimulated genes are activated, such as Mx1, PKR and ISG-15 genes. Conversely, virus-supportive signalling processes activated upon infection are I kappa B kinase/nuclear factor kappa-light-chain-enhancer of activated B cells (IKK/ NF-κB), phosphatidylinositol-3-kinasee/Akt (PI3K/Akt), and the RNA activating factor-1(Raf-1). Specific inhibition of the latter signalling cascade leads to striking impairment of the replication of all influenza A viruses, as a result of nuclear retention of RNPs in late stages of the replication cycle. In this review, the intracellular signaling that associated with IAV infection will be highlighted to realize the appropriate therapeutically strategy against IAV infection.

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Aging is associated with hypermethylation of autophagy genes in macrophages

Cited by 107 publications

References 34 publications

Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt

Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt

Epigenetics Reprogramming of Autophagy is involved in Childhood Acute Lymphatic Leukemi

The Intracellular Signalling that Associated with Influenza A Virus Infection

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