Exercise suppresses mouse systemic AApoAII amyloidosis through enhancement of the p38 MAPK signaling pathway

Abstract

Exercise interventions are beneficial for reducing the risk of age-related diseases, including amyloidosis, but the underlying molecular links remain unclear. Here, we investigated the protective role of interval exercise training in a mouse model of age-related systemic apolipoprotein A-II amyloidosis (AApoAII) and identified potential mechanisms. Mice subjected to sixteen weeks of exercise showed improved whole-body physiologic functions and exhibited substantial inhibition of amyloidosis, particularly in the liver and spleen. Exercise activated the hepatic p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and the downstream transcription factor tumor suppressor p53. This activation resulted in elevated expression and phosphorylation of heat shock protein beta-1 (HSPB1), a chaperone that defends against protein aggregation. In amyloidosis-induced mice, the hepatic p38 MAPK-related adaptive responses were additively enhanced by exercise. We observed that with exercise, greater amounts of phosphorylated HSPB1 accumulated at amyloid deposition areas, which we suspect inhibits amyloid fibril formation. Collectively, our findings demonstrate the exercise-activated specific chaperone prevention of amyloidosis, and suggest that exercise may amplify intracellular stress-related protective adaptation pathways against age-associated disorders such as amyloidosis.

PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast

“…Analysis of mRNA expression was performed as described previously. 28 Total RNA was isolated using TRIzol reagent (Invitrogen) and reverse transcribed using a High Capacity cDNA Reverse Transcription Kit with random primers (Applied Biosystems). Real‐time qPCR was performed using a sequence detection system (Abi Prism 7500, Applied Biosystems) with SYBR Green (TaKaRa Bio).…”

“…Analysis of mRNA expression was performed as described previously 28 . Total RNA was isolated using TRIzol reagent (Invitrogen) and reverse transcribed using a High Capacity cDNA Reverse Transcription Kit with random primers (Applied Biosystems).…”