Occult hepatitis C virus elicits mitochondrial oxidative stress in lymphocytes and triggers PI3-kinase-mediated DNA damage response

Bhargava, Arpit; Raghuram, G.; Pathak, Neelam; Varshney, Subodh; Jatawa, Suresh Kumar; Jain, Deepika; Mishra, Pradyumna Kumar

doi:10.1016/j.freeradbiomed.2011.08.009

Cited by 40 publications

(41 citation statements)

References 43 publications

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“…It has been reported that HCV proteins can move from the ER synthesis site to the mitochondria, therefore, there is an interaction between HCV proteins with the mitochondrial machinery in hepatic and extra-hepatic sites. Impairment of mitochondrianuclear cross talk through involvement of PI3 kinases has been published by Bhargava et al [17] , 2011.…”

Section: Hcv and Oxidative Stressmentioning

confidence: 92%

“…This effect has been associated with a specific regulation of the virus replication cycle [15] . It is reported that viral proteins such as HCV-core, E1, and NS3 can modulate and inactivate mitochondrial respiratory chain enzymes and in turn unshackle blockade of the electrons, disruption of mitochondrial transmembrane potential, and electron leakage inducing an increase of intracellular reactive oxygen species (ROS) levels [16,17] . Together, all these molecular events impair mitochondrial and cellular signaling pathways.…”

Section: Hcv and Oxidative Stressmentioning

confidence: 99%

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Oxidative stress modulation in hepatitis C virus infected cells

Lozano-Sepúlveda

Bryan-Marrugo

Córdova-Fletes

et al. 2015

WJH

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Section: Hcv and Oxidative Stressmentioning

confidence: 92%

Section: Hcv and Oxidative Stressmentioning

confidence: 99%

Oxidative stress modulation in hepatitis C virus infected cells

Lozano-Sepúlveda

Bryan-Marrugo

Córdova-Fletes

et al. 2015

WJH

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“…The mitochondrion plays a pivotal role in cellular homeostasis not only by generating the vast majority of the supply of adenosine triphosphate (ATP), but also by influencing apoptosis, cell cycle, and metabolism [30]. Through aerobic respiration, mitochondria generate ATP that oxidize glucose, pyruvate, and nicotinamide adenine dinucleotide and hydrogen (NADH), and contribute to the formation of reactive oxygen species (ROS) as a byproduct [31]. Under normal physiological circumstances, the deleterious effects caused by the highly reactive nature of ROS are balanced by the presence of antioxidants, including glutathione, carotenoids, and antioxidant enzymes such as superoxide dismutase, glutathione reductase, catalase and glutathione peroxidase [32].…”

Section: Mitochondrial Retrograde Signalingmentioning

confidence: 99%

Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

Mishra¹,

Raghuram²,

Bunkar³

et al. 2015

Int J Occup Med Environ Health

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International Journal of Occupational Medicine and Environmental AbstractDecember 2014 marked the 30th year anniversary of Bhopal gas tragedy. This sudden and accidental leakage of deadly poisonous methyl isocyanate (MIC) gas instigated research efforts to understand the nature, severity of health damage and sufferings of 570 000 ailing survivors of this tragedy. In a decade-long period, our systematic laboratory investigations coupled with long-term molecular surveillance studies have comprehensively demonstrated that the risk of developing an environmental associated aberrant disease phenotype, including cancer, involves complex interplay of genomic and epigenetic reprogramming. These findings poised us to translate this knowledge into an investigative framework of "molecu lar biodosimetry" in a strictly selected cohort of MIC exposed individuals. A pragmatic cancer risk-assessment strategy pursued in concert with a large-scale epidemiological study might unfold molecular underpinnings of host-susceptibility and exposureresponse relationship. The challenges are enormous, but we postulate that the study will be necessary to establish a direct initiation-promotion paradigm of environmental carcinogenesis. Given that mitochondrial retrograde signaling-induced epigenetic reprogramming is apparently linked to neoplasticity, a cutting-edge tailored approach by an expert pool of biomedical researchers will be fundamental to drive these strategies from planning to execution. Validating the epigenomic signatures will hopefully result in the development of biomarkers to better protect human lives in an overburdened ecosystem, such as India, which is continuously challenged to meet population demands. Besides, delineating the mechanistic links between MIC exposure and cancer morbidity, our investigative strategy might help to formulate suitable regulatory policies and measures to reduce the overall burden of occupational and environmental carcinogenesis.

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“…Chronic infections, clinically manifest or subclinical, are an additional interesting condition for virus related DNA damage investigation [37] . In this setting the measurement of chromosomal abnormalities in peripheral blood lymphocytes should result particularly fruitful, if one considers that circulating cells are exposed to infectious agents even in localized infections during tissue perfusion [23,58,59] . Precious information would be generated through the analysis of pre-tumoral and tumoral banked samples, where the observation of abnormal mitosis and genetic abnormalities can be associated with the identification of virus related antigens or nucleic acids [60] , while prospective studies could include virus isolation.…”

Section: Testing the Hypothesismentioning

confidence: 99%

How virus persistence can initiate the tumorigenesis process

Avanzi

Alvisi²,

Ripalti³

2013

WJV

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Human oncogenic viruses are defined as necessary but not sufficient to initiate cancer. Experimental evidence suggests that the oncogenic potential of a virus is effective in cells that have already accumulated a number of genetic mutations leading to cell cycle deregulation. Current models for viral driven oncogenesis cannot explain why tumor development in carriers of tumorigenic viruses is a very rare event, occurring decades after virus infection. Considering that viruses are mutagenic agents per se and human oncogenic viruses additionally establish latent and persistent infections, we attempt here to provide a general mechanism of tumor initiation both for RNA and DNA viruses, suggesting viruses could be both necessary and sufficient in triggering human tumorigenesis initiation. Upon reviewing emerging evidence on the ability of viruses to induce DNA damage while subverting the DNA damage response and inducing epigenetic disturbance in the infected cell, we hypothesize a general, albeit inefficient hit and rest mechanism by which viruses may produce a limited reservoir of cells harboring permanent damage that would be initiated when the virus first hits the cell, before latency is established. Cells surviving virus generated damage would consequently become more sensitive to further damage mediated by the otherwise insufficient transforming activity of virus products expressed in latency, or upon episodic reactivations (viral persistence). Cells with a combination of genetic and epigenetic damage leading to a cancerous phenotype would emerge very rarely, as the probability of such an occurrence would be dependent on severity and frequency of consecutive hit and rest cycles due to viral reinfections and reactivations

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Occult hepatitis C virus elicits mitochondrial oxidative stress in lymphocytes and triggers PI3-kinase-mediated DNA damage response

Cited by 40 publications

References 43 publications

Oxidative stress modulation in hepatitis C virus infected cells

Oxidative stress modulation in hepatitis C virus infected cells

Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

How virus persistence can initiate the tumorigenesis process

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