Autophagy in exposure to environmental chemicals

Jing

et al. 2019

Basic Clin Pharma Tox

Chronic overexposure to manganese (Mn) has been verified to induce mitochondrial dysfunction, which is related to oxidative damage. The autophagic‐lysosomal degradation pathway plays a vital role in the removal of impaired mitochondria through a specific quality control mechanism termed mitophagy. However, trehalose functions as an inducer of autophagy by an mTOR‐independent mechanism, and little data report its effect on Mn‐induced mitochondrial dysfunction. To explore the possibility that trehalose could be effective in interfering with the Mn‐induced mitochondrial dysfunction, we used trehalose (2% and 4% (g/vol (mL))) in a mouse model of manganism. Our data showed that mice developed weary motor and behavioural deficits after exposure to Mn for 6 weeks. Overexposure to Mn resulted in mitochondrial dysfunction and neuronal cell damage in the basal nuclei of mice, which could be ameliorated by trehalose pre‐treatment. Moreover, our results indicated that trehalose pre‐treatment significantly reduced the oxidative damage and enhanced the activation of mitophagy. The findings clearly demonstrated that trehalose could relieve Mn‐induced mitochondrial and neuronal cell damage through its antioxidative and mitophagy‐inducing effects.

Section: Discussionmentioning

confidence: 50%

“…Autophagy is the lysosome‐mediated selective degradation of cellular components for protein recycling to maintain cellular homeostasis . Our results showed that exposure to Mn could stimulate autophagy activation in mice.…”

Section: Discussionmentioning

confidence: 63%

Effect of trehalose on manganese‐induced mitochondrial dysfunction and neuronal cell damage in mice

Jing

et al. 2019

Basic Clin Pharma Tox

“…As recently reviewed, autophagy dysfunction is associated with many of the chemicalinduced cytotoxic mechanisms, including mitochondrial dysfunction, DNA damage, oxidative stress, stress of the endoplasmic reticulum, impairment of lysosomal functions, and inflammation [96]. Focusing on B[a]P, our results would thus tend to suggest that activation of NHE1 might play a role in the control of autophagy.…”

Section: A N U S C R I P Tmentioning

confidence: 65%

“…As recently reviewed, a growing number of environmental pollutants are now known to interfere with autophagy [96]. Non-exhaustively, cadmium [97], arsenic [98], paraquat [99], bisphenol A [100], patulin [101] and TCDD [102,103], have been shown to differentially affect autophagy.…”

Section: -3-1-autophagy: a Key Cellular Process To Cope With Stressfmentioning

confidence: 99%

Disturbances in H+ dynamics during environmental carcinogenesis

et al. 2019

Abbreviations: B[a]P: benzo[a]pyrene; GPCR: G-protein coupled receptor; MCT: monocarboxylate transporter; NHE1: Na + /H + exchanger 1HIGHLIGHTS Benzo[a]pyrene, a well-known environmental carcinogen, alters H + dynamics. NHE1 activation by B[a]P plays a key role in H + dynamics alterations. B[a]P-altered pH controls cell death/survival balance via mitochondria and lysosome. ABSTRACTDespite the improvement of diagnostic methods and anticancer therapeutics, the human population is still facing an increasing incidence of several types of cancers. According to the World Health Organization, this growing trend would be partly linked to our environment, with around 20% of cancers stemming from exposure to environmental contaminants, notably chemicals like polycyclic aromatic hydrocarbons (PAHs). PAHs are widespread pollutants in our environment resulting from incomplete combustion or pyrolysis of organic material, and thus produced by both natural and anthropic sources; notably benzo[a]pyrene (B[a]P), i.e. the prototypical molecule of this family, that can be detected in cigarette smoke, diesel exhaust particles, occupational-related fumes, and grilled food. This molecule is a well-recognized carcinogen belonging to group 1 carcinogens. Indeed, it can target the different steps of the carcinogenic process and all cancer hallmarks. Interestingly, H + dynamics have been described as key parameters for the occurrence of several, if not all, of these hallmarks. However, information regarding the role of such parameters during environmental carcinogenesis is still very scarce. The present review will thus mainly give an overview of the impact of B[a]P on H + dynamics in liver cells, and will show how such alterations might impact different aspects related to the finely-tuned balance between cell death and survival processes, thereby likely favoring environmental carcinogenesis. In total, the main objective of this review is to encourage further research in this poorly explored field of environmental molecular toxicology.

Environmental Toxicology

“…Since autophagy is one of the major intracellular mechanism to eliminate misfolded proteins and maintain proteostasis, it plays a role in preventing the accumulation of α‐Syn leading to its oligomerization and Mn‐induced neurotoxicity. Autophagy can be stimulated in response to various stress conditions, including oxidative stress (increased ROS production), accumulation of unfolded proteins, viral infection, or starvation . Therefore, the regulation of autophagy is proposed as a potential therapeutic avenue for these diseases.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of trehalose against Mn‐induced α‐synuclein oligomerization in mice: Involvement of oxidative stress and autophagy

Jing¹,

Liu²,

Liu³

et al. 2019

Overexposure to manganese (Mn) is widely known to induce alpha-synuclein (α-Syn) oligomerization, which has been attributed to the oxidative damage of α-Syn protein.Trehalose has been shown to induce autophagy and serve as a chemical chaperone, but little information has been reported about its effect on Mn-induced α-Syn oligomerization. In this study, we investigate whether trehalose can effectively interfere with Mn-induced α-Syn oligomerization, using different concentrations of trehalose (2% and 4% (g/vol [mL])) in a mouse model of manganism. After 6 weeks of exposure to Mn, both oxidative stress and autophagy were activated and resulted in α-Syn oligomerization and neuronal cell damage in the mouse brain tissue. Our results also revealed that pretreatment with trehalose significantly reduced the oxidative damage to α-Syn protein and increased autophagy activation. These findings clearly demonstrated that trehalose can relieve Mn-induced α-Syn oligomerization and neuronal cell damage through its anti-oxidative and autophagy-inducing effects. K E Y W O R D Salpha-synuclein oligomerization, autophagy, manganese, oxidive stress, trehalose