Iron and Sphingolipids as Common Players of (Mal)Adaptation to Hypoxia in Pulmonary Diseases.

Abstract

Hypoxia, or lack of oxygen, can occur in both physiological (high altitude) and pathological conditions (respiratory diseases). In this narrative review, we introduce high altitude pulmonary edema (HAPE), acute respiratory distress syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), and Cystic Fibrosis (CF) as examples of maladaptation to hypoxia, and highlight some of the potential mechanisms influencing the prognosis of the affected patients. Among the specific pathways modulated in response to hypoxia, iron metabolism has been widely explored in recent years. Recent evidence emphasizes hepcidin as highly involved in the compensatory response to hypoxia in healthy subjects. A less investigated field in the adaptation to hypoxia is the sphingolipid (SPL) metabolism, especially through Ceramide and sphingosine 1 phosphate. Both individually and in concert, iron and SPL are active players of the (mal)adaptation to physiological hypoxia, which can result in the pathological HAPE. Our aim is to identify some pathways and/or markers involved in the physiological adaptation to low atmospheric pressures (high altitudes) that could be involved in pathological adaptation to hypoxia as it occurs in pulmonary inflammatory diseases. Hepcidin, Cer, S1P, and their interplay in hypoxia are raising growing interest both as prognostic factors and therapeutical targets.

• Authors: Sara Ottolenghi, Aida Zulueta, Anna Caretti
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 1 (Jan 02 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31906427 (Publication Type: Journal Article, Review)

Chemical References

• Ceramides
• Hepcidins
• Lysophospholipids
• Sphingolipids
• sphingosine 1-phosphate
• Iron
• Sphingosine

Topics

• Adaptation, Physiological
• Altitude Sickness (metabolism)
• Ceramides (metabolism)
• Cystic Fibrosis (metabolism)
• Hepcidins (metabolism)
• Humans
• Hypertension, Pulmonary (metabolism)
• Hypoxia (metabolism, physiopathology)
• Iron (metabolism)
• Lysophospholipids (metabolism)
• Pulmonary Disease, Chronic Obstructive (metabolism)
• Respiratory Distress Syndrome (metabolism)
• Sphingolipids (metabolism)
• Sphingosine (analogs & derivatives, metabolism)