Exploring miRNA function in maintaining redox mechanism of high altitude hypoxia associated maladies: An evidence based study

Abstract

The maintenance of balance between pro-oxidants and antioxidants is paramount for healthy aerobic cell status as cell may face oxidative stress if this balance is disturbed. During ascent to high altitude, reactive oxygen species (ROS) is enhanced and antioxidant system declined due to low oxygen availability. A number of evidences suggested the role of high altitude hypoxia in various maladies due to perturbed redox homeostasis. High altitude associated maladies include High Altitude Pulmonary Edema (HAPE), High Altitude Cerebral Edema (HACE), Acute mountain sickness (AMS), chronic mountain sickness (CMS), pulmonary hypertension, venous thrombosis, sleep disorders, muscle atrophy etc. Many supplementations such as vitamin C, vitamin E, resveratrol, β-carotene, quercetin, acetyl-l-carnitine, Ginkgo biloba, N-acetyl cysteine, selenium, Ganoderma lucidum, l-carnosine, ursolic acid have been extensively researched for counteracting the high altitude associated oxidative stress. However, most of the supplementations are having limited beneficial effects. However, miRNA can become an answer for high altitude associated pathophysiological conditions as miRNAs regulate energy metabolism, metabolic pathways, oxidative stress, inflammation etc. On that, miRNAs are easily assessable, highly specific and sensitive small molecules that can also exploited as a biomarker. To consider the seriousness of the problem, the present study screened out the miRNAs that are directly involved in maintaining NADPH oxidases (NOX), nitric oxide synthases (NOS), thioredoxin induced protein (TXNIP) and antioxidants enzymes, comprising superoxide dismutase (SOD), catalase, glutathione peroxidise (GPX), peroxiredoxins (PRDX), thioredoxins (TXN), thioredoxin reductase (TXNRD). After analysis with the screened miRNAs, the extraction of miRNA (12 miRNAs) was done that have role in regulating free radical producing enzymes such as NOS, NOX and TXNIP. It is hypothesized that regulating miRNAs could become a probable answer for high altitude associated maladies. Hence, further research in this direction is required to proof the concept.