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Clock gene protein mPER1 is rhythmically synthesized and under cAMP control in the mouse pineal organ
C von Gall1, I Schneider-Hüther, M Pfeffer
1Institute of Anatomy II, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Abstract:
The mammalian clock gene Per1 is an important element of endogenous oscillators that control daily rhythms in central and peripheral tissues. Although such autonomous clock function is lost in the mammalian pineal gland during evolution, mPer1 mRNA and mPER1 protein were found to be strongly elevated in the mouse pineal organ during the dark period compared to daytime values. In vitro studies showed that mPer1 mRNA and mPER1 protein in mouse pineal gland are induced following the activation of a signalling pathway of fundamental importance for pineal physiology, the norepinephrine/cAMP/phosphoCREB cascade. mPER1 may function in the mouse pineal gland as a time-measuring molecule to participate in regulating rhythmic cellular responses in vivo.
Insights
The mouse pineal gland shows elevated levels of the clock gene Per1 (mPer1) and its protein (mPER1) during darkness. This rhythm is regulated by the norepinephrine/cAMP/phosphoCREB pathway, suggesting mPER1 acts as a time-measuring molecule.
Area of Science:
- Chronobiology
- Molecular Biology
- Mammalian Physiology
Background:
- The mammalian Per1 gene is crucial for daily rhythms in various tissues.
- The pineal gland, while lacking autonomous clock function, exhibits rhythmic expression of mPer1.
- Norepinephrine signaling is vital for pineal gland physiology.
Purpose of the Study:
- To investigate the regulation of mPer1 mRNA and mPER1 protein in the mouse pineal gland.
- To explore the role of the norepinephrine/cAMP/phosphoCREB pathway in mPer1 expression.
- To determine the potential function of mPER1 in the mouse pineal gland.
Main Methods:
- Quantitative analysis of mPer1 mRNA and mPER1 protein levels in mouse pineal glands during light and dark periods.
- In vitro studies stimulating the norepinephrine/cAMP/phosphoCREB signaling pathway.
- Assessment of mPER1's role in regulating rhythmic cellular responses.
Main Results:
- mPer1 mRNA and mPER1 protein levels were significantly higher in the mouse pineal gland during the dark phase compared to the light phase.
- Activation of the norepinephrine/cAMP/phosphoCREB cascade in vitro led to increased mPer1 mRNA and mPER1 protein.
- mPER1 was identified as a potential time-measuring molecule involved in pineal gland cellular rhythm regulation.
Conclusions:
- The mouse pineal gland exhibits a circadian rhythm in mPer1 expression, despite lacking autonomous clock function.
- The norepinephrine/cAMP/phosphoCREB pathway is a key regulator of mPer1 expression in the pineal gland.
- mPER1 likely plays a role in mediating rhythmic cellular functions within the mouse pineal gland.