MKK3 influences mitophagy and is involved in cigarette smoke-induced inflammation

Mannam, Praveen; Rauniyar, Navin; Lam, TuKiet T.; Luo, Ruiyan; Lee, Patricia; Srivastava, Anup

doi:10.1016/j.freeradbiomed.2016.10.001

Cited by 26 publications

(16 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is much evidence to show that chronic systemic inflammation has a major role in the development of atherosclerosis [ 13 , 14 , 15 ]. The effects of the CSon systemic inflammatory response is well defined in several studies [ 16 , 17 , 18 ]. In a multi-ethnic cohort study, both former and current CS were found to be independently associated with markers of inflammation and subclinical atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

A New Inflammatory Marker: Elevated Monocyte to HDL Cholesterol Ratio Associated with Smoking

Yılmaz

Kayançiçek

2018

JCM

View full text Add to dashboard Cite

Objectives: The adverse effects of smoking in various pathologies are mediated by its effects on the inflammatory system. The monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) has recently emerged as an indicator of inflammation. We aimed to investigate the relationship between MHR and cigarette smoking. Patients and Methods: Three hundred and ninety seven consecutive participants who smoke and 515 healthy subjects with no history of smoking enrolled in the study. Complete blood count parameters and lipid profile were analyzed in all study participants. Smoking habits were calculated as pack.years and number of cigarettes smoked per day. Results: MHR levels were significantly higher in smokers compared to non-smokers (respectively, 15.71 (12.02–20.00) and 11.17 (8.50–14.16), p < 0.0001)). Pearson’s correlation analysis revealed a weak but positive correlation between pack.year and MHR in the smokers group, and there was a moderate positive correlation between the number of cigarettes smoked daily and MHR in the group. In receiver operating characteristics (ROC) analyses, it was determined that a MHR value >13.00 measured in smoker participants at application had a predictive specificity of 66.6% and sensitivity of 70.0% for smoking (area under the curve [AUC] 0.729, 95% CI 0.696, 0.762; p < 0.0001). Conclusions: Elevated MHR is associated with cigarette smoking and may be a useful indicator of a systemic inflammatory response in smokers. Smoker participants who have high MHR levels can easily be identified during routine complete blood count (CBC) analysis and could possibly benefit from preventive treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

A New Inflammatory Marker: Elevated Monocyte to HDL Cholesterol Ratio Associated with Smoking

Yılmaz

Kayançiçek

2018

JCM

View full text Add to dashboard Cite

show abstract

“…Smokers have a higher risk of developing high-frequency hearing loss than non-smokers with a similar occupational noise exposure 92, 93 . The interaction may be related to a dual insult to mitochondria, since animal experiments have documented that exposure to cigarette smoke leads to the generation of oxidative stress by affecting mitochondrial function 94 .…”

Section: Human Studiesmentioning

confidence: 99%

Emerging therapeutic interventions against noise-induced hearing loss

Sha

Schacht

2016

Expert Opinion on Investigational Drugs

105

View full text Add to dashboard Cite

Introduction Noise-induced hearing loss (NIHL) due to industrial, military, and recreational noise exposure is a major, but also potentially preventable cause of acquired hearing loss. For the United States it is estimated that 26 million people (15% of the population) between the ages of 20 and 69 have a high-frequency NIHL at a detriment to the quality of life of the affected individuals and great economic cost to society. Areas covered This review outlines the pathology and pathophysiology of hearing loss as seen in humans and animal models. Results from molecular studies are presented that have provided the basis for therapeutic strategies successfully applied to animals. Several compounds emerging from these studies (mostly antioxidants) are now being tested in field trials. Expert opinion Although no clinically applicable intervention has been approved yet, recent trials are encouraging. In order to maximize protective therapies, future work needs to apply stringent criteria for noise exposure and outcome parameters. Attention needs to be paid not only to permanent NIHL due to death of sensory cells but also to temporary effects that may show delayed consequences. Existing results combined with the search for efficacious new therapies should establish a viable treatment within a decade.

show abstract

“…Thus, it is crucial to investigate the autophagy process in its entirety, which is collectively termed as ‘autophagy-flux’, and mere detection of autophagosomes and the quantification of LC3 processing is an inadequate and misleading methodology for the accurate evaluation of the autophagy response against external insults such as chronic CS [12, 34]. In addition, recent studies also emphasize the role of mitophagy, a form of autophagy that selectively degrades dysfunctional mitochondria, in COPD-emphysema [29, 35–37]. It is suggested that CS-induced mitochondrial-dysfunction [29, 36–38] and insufficient mitophagy collectively contributes to lung cellular senescence and progression of COPD [39], while augmenting mitophagy in human lung fibroblasts reduces or inhibits accumulation of damaged mitochondria and the resulting cellular senescence, suggesting a therapeutic benefit in COPD subjects [39].…”

Section: Introductionmentioning

confidence: 99%

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology

Bodas

Vij

2017

Respir Res

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

show abstract

MKK3 influences mitophagy and is involved in cigarette smoke-induced inflammation

Cited by 26 publications

References 76 publications

A New Inflammatory Marker: Elevated Monocyte to HDL Cholesterol Ratio Associated with Smoking

A New Inflammatory Marker: Elevated Monocyte to HDL Cholesterol Ratio Associated with Smoking

Emerging therapeutic interventions against noise-induced hearing loss

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology

Contact Info

Product

Resources

About