Crosstalk of autophagy and apoptosis: Involvement of the dual role of autophagy under ER stress

Song, Shuling; Tan, Jin; Miao, Yuyang; Li, Mengmeng; Zhang, Qiang

doi:10.1002/jcp.25785

Cited by 439 publications

(311 citation statements)

References 46 publications

Supporting

Mentioning

296

Contrasting

Unclassified

Order By: Relevance

“…The inability of cells to remove damaged proteins from the ER for a prolonged period of time triggers an apoptotic cell death pathway (Hiramatsu et al, 2015;Song et al, 2017). A similar observation was made in vitro when cells were exposed to high levels of oxidised amino acids to generate oxidised proteins (Dunlop et al, 2008) suggesting that oxidised proteins can also trigger apoptotic cell death in a similar way.…”

Section: Discussionsupporting

confidence: 50%

Oxidised protein metabolism: recent insights

Samardzic

Rodgers

2017

Biological Chemistry

View full text Add to dashboard Cite

Abstract:The 'oxygen paradox' arises from the fact that oxygen, the molecule that aerobic life depends on, threatens its very existence. An oxygen-rich environment provided life on Earth with more efficient bioenergetics and, with it, the challenge of having to deal with a host of oxygen-derived reactive species capable of damaging proteins and other crucial cellular components. In this minireview, we explore recent insights into the metabolism of proteins that have been reversibly or irreversibly damaged by oxygen-derived species. We discuss recent data on the important roles played by the proteasomal and lysosomal systems in the proteolytic degradation of oxidatively damaged proteins and the effects of oxidative damage on the function of the proteolytic pathways themselves. Mitochondria are central to oxygen utilisation in the cell, and their ability to handle oxygen-derived radicals is an important and still emerging area of research. Current knowledge of the proteolytic machinery in the mitochondria, including the ATPdependent AAA+ proteases and mitochondrial-derived vesicles, is also highlighted in the review. Significant progress is still being made in regard to understanding the mechanisms underlying the detection and degradation of oxidised proteins and how proteolytic pathways interact with each other. Finally, we highlight a few unanswered questions such as the possibility of oxidised amino acids released from oxidised proteins by proteolysis being re-utilised in protein synthesis thus establishing a vicious cycle of oxidation in cells.

show abstract

Section: Discussionsupporting

confidence: 50%

Oxidised protein metabolism: recent insights

Samardzic

Rodgers

2017

Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Due to oxidative stress reactions in IRI, the increasing intracellular ROS level stimulates mitochondria-mediated apoptosis. Caspase-8 and caspase-9 are two important indicators of mitochondria-mediated apoptosis [51, 52], and our results showed that RSV downregulated both factors in vivo and in vitro , indicating that RSV reduced cell apoptosis by downregulating the caspase cascade. The caspase cascade also includes another effector, caspase-3, which can be activated in IRI and directly mediates cell apoptosis.…”

Section: Discussionmentioning

confidence: 80%

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Wang

et al. 2018

Cell Physiol Biochem

100

View full text Add to dashboard Cite

Background: Ischemia-reperfusion injury (IRI) is one of the major causes of postoperative renal allograft dysfunction, which is mainly the result of proinflammatory reactions including inflammatory responses, oxidative stress, and metabolic disorders. Resveratrol (RSV) plays an important role in protecting various organs in IRI because it reduces oxidative stress, lessens the inflammatory response, and exerts anti-apoptotic effects. The aim of this study was to demonstrate the renoprotective effect of RSV in inhibiting inflammatory responses, reducing oxidative stress, and decreasing cell apoptosis in vivo and in vitro. Methods: RSV was administered before renal ischemia and H₂O₂ induction. Serum and kidneys were harvested 24 h after reperfusion and NRK-52E cells were collected 4 h after H₂O₂ stimulation. Serum creatinine and blood urea nitrogen were used to assess renal function. Hematoxylin and eosin staining was performed to assess histological injury. Quantitative real-time PCR and enzyme-linked immunosorbent assay were used to assess proinflammatory cytokine expression. Oxidative stress–related proteins, such as Nrf2 and TLR4, were evaluated by western blot. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling assay was used to detect apoptotic cells in tissues, and western blot was used to evaluate the expression of caspase-3, -8, and -9 in this study. Results: RSV inhibited inflammatory responses and improved renal function after renal IRI. Additionally, RSV decreased oxidative stress and reduced cell apoptosis by upregulating Nrf2 expression, downregulating the TLR4/NF-κB signaling pathway, and by decreasing caspase-3 activity and caspase cascades. Conclusion: Our study demonstrated the mechanisms underlying RSV renoprotection. We found that RSV exerts its greatest effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the Nrf2/TLR4/NF-κB pathway.

show abstract

“…Generally, autophagy blocks the induction of apoptosis and inhibits the activation of apoptosis‐associated caspase which could reduce cellular injury 45. However, in special cases, autophagy or autophagy‐relevant proteins may help to induce apoptosis, which could aggravate cell damage 46. Therefore, it is not surprising that many scholars have drawn opposite conclusions about the role of autophagy in various acute injuries.…”

Section: Discussionmentioning

confidence: 99%

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Zhou

Fan

Zhong

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

The ability of cisplatin (cis‐diamminedichloroplatinum II) toxicity to induce acute kidney injury (AKI) has attracted people's attention and concern for a long time, but its molecular mechanisms are still widely unknown. We found that the expression of transforming growth factor‐β (TGF‐β)‐activated kinase 1 (TAK1) could be increased in kidneys of mice administrated with cisplatin. Autophagy is an evolutionarily conserved catabolic pathway and is involved in various acute and chronic injuries. Moreover, p38 MAPK (mitogen‐activated protein kinase) and ERK regulate autophagy in response to various stimuli. Therefore, our hypothesis is that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells and thus exacerbating kidney damage. Here, BALB/c mice were intraperitoneally injected with a TAK1 inhibitor and were then administrated with sham or cisplatin at 20 mg/kg by intraperitoneal injection. Compared with mice in the vehicle cisplatin group, mice intraperitoneally injected with a TAK1 inhibitor were found to have lower serum creatinine and less tubular damage following cisplatin‐induced AKI. Furthermore, inhibition of TAK1 reduced p38 and Erk phosphorylation, decreased expression of LC3II and reversed the down‐regulation of P62 expression induced by cisplatin. The hypothesis was verified with tubular epithelial cells administrated with cisplatin in vitro. Finally, p38 inhibitor or ERK inhibitor abated autophagy activation and cell viability reduction in tubular epithelial cells treated with cisplatin plus TAK1 overexpression vector. Taken together, our results show that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells that exacerbates kidney damage.

show abstract

Crosstalk of autophagy and apoptosis: Involvement of the dual role of autophagy under ER stress

Cited by 439 publications

References 46 publications

Oxidised protein metabolism: recent insights

Oxidised protein metabolism: recent insights

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Contact Info

Product

Resources

About