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Aging aggravated liver ischemia and reperfusion injury by promoting hepatocyte necroptosis in an endoplasmic reticulum stress-dependent manner
- Source :
- Ann Transl Med
- Publication Year :
- 2020
- Publisher :
- AME Publishing Company, 2020.
-
Abstract
- Background Aggravated liver ischemia and reperfusion (IR) injury has been reported in aged mice. Although necroptosis inhibition showed no crucial effect on hepatic IR injury in young mice, whether and how necroptosis affects liver IR injury in aged mice remains unclear. Methods Young and aged mice were subjected to liver IR modeling. Liver injury, hepatocyte necroptosis and endoplasmic reticulum (ER) stress were analyzed in different groups. Results Significantly increased liver necroptosis was found in aged mice post IR compared with young mice. Necroptosis inhibition by necrostatin-1 (Nec-1) decreased hepatocyte necroptosis and liver injury post IR in aged mice, with no significant effects on young mice. Furthermore, IR induced ER stress in both young and aged mice, and enhanced ER stress was observed in aged mice post IR. Administration of 4-phenylbutyrate (4-PBA), an ER stress antagonist, alleviated liver IR injury in both young and aged mice. However, ER stress inhibition reduced hepatocyte necroptosis in aged mice but not in young mice. Conclusions Aging increased ER stress in IR-stressed hepatocytes, leading to aggravated necroptosis and liver IR injury. Our study demonstrated a novel mechanism of ER stress in the regulation of hepatocyte necroptosis in aged livers post IR, which would be a potential therapeutic target to reduce liver IR injury in elderly patients.
- Subjects :
- 0301 basic medicine
Liver injury
medicine.medical_specialty
business.industry
Endoplasmic reticulum
Necroptosis
Antagonist
General Medicine
medicine.disease
Liver ischemia
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
Endocrinology
Internal medicine
Hepatocyte
medicine
Unfolded protein response
Original Article
business
Reperfusion injury
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 23055847 and 23055839
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Annals of Translational Medicine
- Accession number :
- edsair.doi.dedup.....bda4a3b44a210a250e6753ba1ac300f8