Acute Hypobaric Hypoxia-Mediated Biochemical/Metabolic Shuffling and Differential Modulation of S1PR-SphK in Cardiac and Skeletal Muscles.

Abstract

High altitude exposure alters biochemical, metabolic, and physiological features of heart and skeletal muscles, and hence has pathological consequences in these tissues. Central to these hypoxia-associated biochemical/metabolic shuffling are energy deficit accumulation of free radicals and ensuing oxidative damage in the tissue. Recent preclinical/clinical studies indicate sphingosine-1-phosphate (S1P) axis, comprising S1P G protein coupled receptors (S1PR1-5) and its synthesizing enzyme-sphingosine kinase (SphK) to have key regulatory roles in homeostatic cardiac and skeletal muscle biology. In view of this, the aim of the present study was to chart the initiation and progression of biochemical/metabolic shuffling and assess the coincident differential modulation of S1PR(1-5) expression and total SphK activity in cardiac and skeletal muscles from rats exposed to progressive hypobaric hypoxia (HH; 21,000 feet for 12, 24, and 48 hours). HH-associated responses were evident as raised damage markers in plasma, oxidative stress, decreased total tissue protein, imbalance of intermediate metabolites, and aerobic/anaerobic enzyme activities in cardiac and skeletal muscles (gastrocnemius and soleus) culminating as energy deficit. Cardiac and gastrocnemius muscles were more susceptible to hypoxic environment than soleus muscle. These differential responses were directly and indirectly coincident with temporal expression of S1PR(1-5) and SphK activity.