TY - JOUR
T1 - Behavioral stress reduces RIP140 expression in astrocyte and increases brain lipid accumulation
AU - Feng, Xudong
AU - Lin, Yu Lung
AU - Wei, Li Na
N1 - Funding Information:
This work was supported by DK54733 , DK60521 , DK54733-11S , Dean’s Commitment, and the Distinguished McKnight Professorship of University of Minnesota to LNW.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5
Y1 - 2015/5
N2 - Receptor-interacting protein 140 (RIP140) is highly expressed in the brain, and acts in neurons and microglia to affect emotional responses. The present study reveals an additional function of RIP140 in the brain, which is to regulate brain lipid homeostasis via its action in astrocytes. We found forced swim stress (FSS) significantly reduces the expression level of RIP140 and elevates cholesterol content in the brain. Mechanistically, FSS elevates endoplasmic reticulum stress, which suppresses RIP140 expression by increasing microRNA 33 (miR33) that targets RIP140 mRNA's 3'-untranslated region. Consequentially, cholesterol biosynthesis and export are dramatically increased in astrocyte, the major source of brain cholesterol. These results demonstrate that RIP140 plays an important role in maintaining brain cholesterol homeostasis through, partially, regulating cholesterol metabolism in, and mobilization from, astrocyte. Altering RIP140 levels can disrupt brain cholesterol homeostasis, which may contribute to behavioral stress-induced neurological disorders.
AB - Receptor-interacting protein 140 (RIP140) is highly expressed in the brain, and acts in neurons and microglia to affect emotional responses. The present study reveals an additional function of RIP140 in the brain, which is to regulate brain lipid homeostasis via its action in astrocytes. We found forced swim stress (FSS) significantly reduces the expression level of RIP140 and elevates cholesterol content in the brain. Mechanistically, FSS elevates endoplasmic reticulum stress, which suppresses RIP140 expression by increasing microRNA 33 (miR33) that targets RIP140 mRNA's 3'-untranslated region. Consequentially, cholesterol biosynthesis and export are dramatically increased in astrocyte, the major source of brain cholesterol. These results demonstrate that RIP140 plays an important role in maintaining brain cholesterol homeostasis through, partially, regulating cholesterol metabolism in, and mobilization from, astrocyte. Altering RIP140 levels can disrupt brain cholesterol homeostasis, which may contribute to behavioral stress-induced neurological disorders.
KW - Astrocyte
KW - Cholesterol
KW - RIP140
KW - Stress
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U2 - 10.1016/j.bbi.2015.02.008
DO - 10.1016/j.bbi.2015.02.008
M3 - Article
C2 - 25697398
AN - SCOPUS:84928826441
SN - 0889-1591
VL - 46
SP - 270
EP - 279
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -