Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response

Abstract

Excessive production of unsaturated aldehydes from oxidized lipoproteins and membrane lipids is a characteristic feature of cardiovascular disease. Our previous studies show that unsaturated lipid peroxidation-derived aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) promote autophagy in rat aortic smooth muscle cells (RASMC). In this study, we examined the mechanism by which HNE induces autophagy. Exposure of RASMC to HNE led to the modification of several proteins, most of which were identified by mass spectrometry and confocal microscopy to be localized to the endoplasmic reticulum (ER). HNE stimulated the phosphorylation of PKR-like ER kinase and eukaryotic initiation factor 2α and increased heme oxygenase-1 (HO-1) abundance. HNE treatment also increased LC3-II formation and the phosphorylation of JNK and p38. Pharmacological inhibition of JNK, but not p38, prevented HNE-induced HO-1 expression and LC3-II formation. Inhibition of JNK increased cell death in HNE-treated cells. Pretreatment with the chemical chaperone phenylbutryic acid prevented LC3-II formation as well as JNK phosphorylation and HO-1 induction. Taken together, these data suggest that autophagic responses triggered by unsaturated aldehydes could be attributed, in part, to ER stress, which stimulates autophagy by a JNK-dependent mechanism and promotes cell survival during oxidative stress.

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References 57

1. 1.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

2. 2.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

3. 3.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

4. 4.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

5. 5.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

6. 6.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

7. 7.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

8. 8.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

9. 9.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

10. 10.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

11. 11.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

12. 12.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

13. 13.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

14. 14.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

15. 15.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

16. 16.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

17. 17.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

18. 18.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

19. 19.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

20. 20.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

21. 21.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

22. 22.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

23. 23.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

24. 24.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

25. 25.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

26. 26.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

27. 27.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

28. 28.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

29. 29.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

30. 30.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

31. 31.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

32. 32.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

33. 33.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

34. 34.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

35. 35.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

36. 36.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

37. 37.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

38. 38.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

39. 39.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

40. 40.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

41. 41.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

42. 42.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

43. 43.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

44. 44.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

45. 45.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

46. 46.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

47. 47.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

48. 48.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

49. 49.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

50. 50.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

51. 51.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

52. 52.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

53. 53.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

54. 54.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

55. 55.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

56. 56.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

57. 57.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

Cited by papers we hold 11

• Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications · 2024
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• Autophagy mediates an amplification loop during ferroptosis · 2023
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• Non-coding RNAs and ferroptosis: potential implications for cancer therapy · 2022
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• Oxidative Stress in Autism Spectrum Disorder—Current Progress of Mechanisms and Biomarkers · 2022
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• Interplay Between Lipid Metabolism and Autophagy · 2020
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• Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis · 2019
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• The molecular machinery of regulated cell death · 2019
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• Defective Autophagy in Atherosclerosis: To Die or to Senesce? · 2018
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• Mammalian Metallothionein-2A and Oxidative Stress · 2016
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• Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal · 2014
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• Launch of Redox Biology: A new venue for studies in translational, basic and applied research in the fields of antioxidants, cell signaling and redox therapeutics · 2013
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