An AMPK paradox in pulmonary arterial hypertension
نویسندگان
چکیده
Adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric serine-threonine kinase important as a metabolic sensor for intracellular ATP levels and plays a key role in regulating cell survival and proliferation, particularly when cells are exposed to hypoxia. AMPK is critical for lung function, and abnormal AMPK signaling participates in many lung diseases. Recent studies suggest that both inhibition and activation of AMPK are preventive for the development of pulmonary arterial hypertension (PAH). However, the molecular mechanisms by which inhibition or activation of AMPK affects pulmonary hypertension (PH) appear to be distinct. Inhibition of AMPK by compound C blocks hypoxia-induced autophagy and induces apoptosis in pulmonary artery smooth muscle cells, leading to prevention of PAH; activation of AMPK by metformin attenuates the PH phenotype induced by hypoxia by regulating endothelial cell function. These seemingly opposing data on the function of AMPK in PH can be partly explained by off-target and compartment-specific effects of AMPK inhibitors and activators and the differentiated expression of AMPK in various cell types and subcellular locations. To elucidate the specific roles of AMPK in the pathogenesis of PAH, it is important to study the role of AMPK in a tissue specific manner combining genetic and biochemical approaches.
منابع مشابه
AMP‐activated protein kinase inhibits Kv1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation
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