Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0001339 (
acute pancreatitis
)
10,593
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The circadian clock, a biochemical oscillator, plays a fundamental role in health and diseases. Ferroptosis, a type of regulated cell death driven by oxidative stress, is a prominent feature in iron-induced tissue injury. However, whether an impaired circadian clock contributes to ferroptosis-induced sterile inflammation remains unknown. Here, we show that the circadian transcription factor ARNTL (also known as BMAL1) protects against experimental
acute pancreatitis
through blocking the ferroptosis-mediated release of HMGB1, a mediator of sterile inflammation. We utilized a Cre/LoxP system to generate mice with a specific depletion of Arntl in the pancreas (Pdx1-Cre;Arntl
flox/flox
). These Arntl-deficient mice developed l-arginine-induced
acute pancreatitis
more rapidly than controls, with increased mortality, tissue injury, neutrophil infiltration, and HMGB1 release. In contrast, the administration of liproxstatin-1 (a ferroptosis inhibitor) or anti-HMGB1 neutralizing antibody attenuated the development of
acute pancreatitis
in the Arntl-deficient mice. Mechanistically, pancreatic ARNTL is a key regulator of the expression of multiple antioxidant or membrane repair systems (e.g., SLC7A11, GPX4, SOD1,
TXN
, NFE2L2, and CHMP5) to suppress ferroptotic tissue injury. Collectively, these findings uncover a novel link between the circadian clock and ferroptotic response in inflammation and pancreatic injury.
...
PMID:The circadian clock protects against ferroptosis-induced sterile inflammation. 3211 46
