Rev-Erb

2022-05-19: reference:

Rev-Erb(A) (α/β) #

Rev-Erbα (NR1D) and Rev-Erbβ (NR1D2) (aka αβ). Nuclear receptor transcription factors for the circadian clock.

• Rev-Erbα is also expressed in muscle, adipose tissue, and liver. Regulates Fatty Acid Synthase.
• TLR4 antagonist.
• Detects Heme, its endogenous ligand. Whatever that’s worth.
• Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy
  • Activates the Stk11–AMPK–SIRT1–PGC-1α signaling pathway.
    • Indeed, STK11 (aka LKB1 (liver kinase B)) activates AMPK. mRNA levels are Increased by ERα activation.
  • Inhibits mitophagy. (Thereby increasing mitochondrial content and oxidative capacity of myocytes)
  • A Rev-erb-α/Ppargc1-α cross-talk pathway regulates heme synthesis in hepatic cells:
  • increase in glutamate-malate-stimulated and ADP-driven respiration in absence and presence of succinate of permeabilized fibers
  • Represses genes involved in autophagosome formation and lysosomal degradation.
• Nuclear receptor Rev-erbα: up, down, and all around (2014)
• Nuclear receptor Rev-erbα: a heme receptor that coordinates circadian rhythm and metabolism (2010)
  • Rev-Erb α dimers on RORE recruit NCoR (nuclear corepressor 1) in a Heme-dependent manner. NCoR recruits HDAC3
  • Heme binding to Rev-Erbα induces feedback inhibition of its own synthesis (reducing ALAS1, via NPAS2/PGC-1α)
  • In Brown Adipose (but not the liver), it promotes UCP1.
  • Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function
    • Peaks in the liver (and brown adipose tissue. Wonder about the brain?) at mouse ZT 10 (and α is a bit higher): but so what, is this equivalent to 2 hours (before? After?) waking for humans? Considering that’s probably when they get up to start the day night.
  • Behavioral Changes and Dopaminergic Dysregulation in Mice Lacking the Nuclear Receptor Rev-erbα
    • Deficient mice had upregulation of Tyrosine Hydroxylase, leading to increased hippocampal dopamine turnover. This lead to hyperlocomotion.
      • This one is kind of surprising, maybe. Why does it repress TH?
    • Decreased habituation in novel object paradigms and impaired short- and long-term memory.

Rev-Erb β #

• Was originally thought to be reduntant, but it does have some distinct actions apparently.