Noradrenaline enhances Na ‐K ATPase subunit expression by HuR‐induced mRNA stabilization and their transportation to the cell surface through PLC and PKC mediated pathway: Implications with REMS‐loss associated disorders

Rapid eye movement sleep deprivation associated elevated noradrenaline (NA) increases nucleus-to-cytoplasmic translocation of HuR. The latter then decreases degradation of the Na-K ATPase mRNA, resulting in stability of its mRNA, which in turn increased its translation without increasing the transcription. The increased Na-K ATPase subunit are then translocated to the neuronal membrane. Our findings not only explain a fundamental molecular mechanism of Na-K ATPase subunit expression, but it may also be exploited to ameliorate REMS-loss associated symptoms and disorders. AbstractRapid eye movement sleep (REMS) maintains brain excitability at least by regulating Na-K ATPase activity. Although REMS deprivation (REMSD)-associated elevated noradrenaline (NA) increases Na-K ATPase protein expression, its mRNA transcription did not increase. We hypothesized and confirmed both in  vivo as well as in vitro that elevated mRNA stability explains the apparent puzzle. The mRNA stability was measured in control and REMSD rat brain with or without in vivo treatment with α1-adrenoceptor (AR) antagonist, prazosin (PRZ). Upon REMSD, Na-K ATPase α1-, and α2-mRNA stability increased significantly, which was prevented by PRZ. To decipher the molecular mechanism of action, we estimated NA-induced Na-K ATPase mRNA stability in Neuro-2a cells under controlled conditions and by transcription blockage using Actinomycin D (Act-D). NA increased Na -K ATPase mRNA stability, which was prevented by P...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research