Autophagy: A Cellular Guardian against Hepatic Lipotoxicity

Sinha, Rohit Anthony

doi:10.3390/genes14030553

Cited by 9 publications

(5 citation statements)

References 131 publications

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“…Our results showed that, indeed, similar to its effect on cellular viability, the targeted degradation of eRNA by RNase 1 significantly reduced the PA induced activation of JNK, its downstream target c-jun, and p38MAPK (Figure 1 E-J). Furthermore, Rnase 1 treatment also rescued PA induced autophagy block which is a major mediator of lipotoxicity [28] (Supplementary Figure 2). To verify if the observed effects of RNase 1 are specifically due to its effects on eRNA, we also used a pharmacological inhibitor of TLR3, a receptor of eRNA and observed a similar rescue effect on PA induced cell death (Figure 1K).…”

Section: Rnase 1 Attenuates Pa Induced Cellular Injury In Hepg2 Cellsmentioning

confidence: 88%

Targeting Extracellular RNA Mitigates Hepatic Lipotoxicity and Liver Injury in NASH

Tewari¹,

Rajak²,

Raza³

et al. 2023

Preprint

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Non-alcoholic steatohepatitis (NASH) is a clinically serious stage of non-alcoholic fatty liver disease (NAFLD). Histologically characterized by hepatocyte ballooning, immune cell infiltration and fibrosis, NASH at a molecular level involves lipid induced hepatocyte death and cytokine production. Currently, there are very few diagnostic biomarkers available to screen NASH, and no pharmacological intervention is available for its treatment. In this study, we show that hepatocyte damage by lipotoxicity results in the release of extracellular RNAs (eRNAs) which serve as damage-associated molecular patterns (DAMPs) that stimulate the expression of pro-apoptotic and pro-inflammatory cytokines, aggravating inflammation, and cell death in HepG2 cells. Furthermore, the inhibition of eRNA activity by RNase 1 significantly increased cellular viability and reduced NF-kB mediated cytokine production. Similarly, RNase 1 administration significantly improved hepatic steatosis, inflammatory and injury markers in a murine NASH model. This study, therefore, for the first time, underscores the therapeutic potential of inhibiting eRNA action as a novel strategy for NASH treatment.

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Section: Rnase 1 Attenuates Pa Induced Cellular Injury In Hepg2 Cellsmentioning

confidence: 88%

Targeting Extracellular RNA Mitigates Hepatic Lipotoxicity and Liver Injury in NASH

Tewari¹,

Rajak²,

Raza³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Notably, although RNase 1 restored p-JNK and p-p38MAPK back to the control levels, its effect did not restore p-c-JUN back to the control levels even though p-c-JUN levels were significantly rescued in RNase 1 and PA-treated cells. Furthermore, the RNase 1 treatment also rescued PA-induced autophagy block, which is a major mediator of lipotoxicity [29] (Supplementary Figure S2). To verify if the observed effects of RNase 1 are specifically due to its effects on eRNA, we also used a pharmacological inhibitor of TLR3, which is a receptor of eRNA, and observed a similar rescue effect on PA-induced cell death (Figure 1L).…”

Section: Rnase 1 Attenuates Pa-induced Cellular Injury In Hepg2 Cellsmentioning

confidence: 88%

Targeting Extracellular RNA Mitigates Hepatic Lipotoxicity and Liver Injury in NASH

Tewari

Rajak

Raza

et al. 2023

Cells

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Non-alcoholic steatohepatitis (NASH) is a clinically serious stage of non-alcoholic fatty liver disease (NAFLD). Histologically characterized by hepatocyte ballooning, immune cell infiltration, and fibrosis, NASH, at a molecular level, involves lipid-induced hepatocyte death and cytokine production. Currently, there are very few diagnostic biomarkers available to screen for NASH, and no pharmacological intervention is available for its treatment. In this study, we show that hepatocyte damage induced by lipotoxicity results in the release of extracellular RNAs (eRNAs), which serve as damage-associated molecular patterns (DAMPs) that stimulate the expression of pro-apoptotic and pro-inflammatory cytokines, aggravate inflammation, and lead to cell death in HepG2 cells. Furthermore, the inhibition of eRNA activity by RNase 1 significantly increases cellular viability and reduces NF-kB-mediated cytokine production. Similarly, RNase 1 administration significantly improves hepatic steatosis, inflammatory and injury markers in a murine NASH model. Therefore, this study, for the first time, underscores the therapeutic potential of inhibiting eRNA action as a novel strategy for NASH treatment.

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“…Відомо препарати, які використовуються в сучасній фармакотерапії, можуть індукувати або пригнічувати протікання (тривалість) аутофагії [57]. Є дані про цільовий вплив на аутофагію (стимуляція і пригнічення) за певних захворювань легень, печінки, нейродегенеративних та інфекційних хвороб [58][59][60][61][62][63].…”

Section: цільовий вплив на аутофагію в умовах різних захворюваньunclassified

Biomedical significance of the therapeutic use of autophagy (literature review)

Sribna

2024

ECM

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Autophagy, or is an intracellular degradation pathway for improperly functioning aggre-gation-prone proteins, damaged organelles, unwanted macromolecules, and invading patho-gens. The process is necessary for maintaining cell and tissue homeostasis, which contributes to the survival of the organism, and is actively studied. The purpose of this work was the search, selection and analysis of the literature on autophagy as one of the main mechanisms of maintaining cellular homeostasis under conditions of oxidative stress; cellular aging; calo-rie restriction; as well as about the targeted effect on autophagy in the conditions of various diseases. The following generalizations were made: 1) the ability to be directly activated in response to the intense formation of reactive oxygen species in cells allows us to consider autophagy as an important element of antioxidant protection, therefore, the study of ways and means of effective autophagy management is becoming relevant today; 2) dietary con-sumption of autophagy activators may promote health and extend lifespan through multiple mechanisms, including reduction of oxidative stress, induction of autophagy, and suppression of inflammation; 3) studies aimed at elucidating the role of sirtuins, which are key regulators of cellular metabolism and oxidative stress, are gaining relevance in the initiation of autoph-agy. Currently, sirtuin-dependent mechanisms of autophagy require research in experimental models using mammalian cells; 4) continuing the study of autophagy processes will allow a better understanding of physiological aspects and help ensure progress in the development of new strategies for the prevention and treatment of human diseases (including those related to age); 5) autophagy is crucial for cellular physiology, autophagy dysfunction is in-volved in the pathogenesis of various human diseases, and therefore the therapeutic use of autophagy has potential biomedical significance. Keywords: cell death, cellular homeostasis, oxidative stress, cellular aging, calorie restriction, targeted effect on autophagy.

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Autophagy: A Cellular Guardian against Hepatic Lipotoxicity

Cited by 9 publications

References 131 publications

Targeting Extracellular RNA Mitigates Hepatic Lipotoxicity and Liver Injury in NASH

Targeting Extracellular RNA Mitigates Hepatic Lipotoxicity and Liver Injury in NASH

Targeting Extracellular RNA Mitigates Hepatic Lipotoxicity and Liver Injury in NASH

Biomedical significance of the therapeutic use of autophagy (literature review)

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