Up-Regulation of Antioxidant Proteins in the Plasma Proteome during Saturation Diving: Unique Coincidence under Hypobaric Hypoxia

Abstract

Saturation diving (SD) is one of the safest techniques for tolerating hyperbaric conditions for long durations. However, the changes in the human plasma protein profile that occur during SD are unknown. To identify differential protein expression during or after SD, 65 blood samples from 15 healthy Japanese men trained in SD were analyzed by two-dimensional fluorescence difference gel electrophoresis. The expression of two proteins, one 32.4 kDa with an isoelectric point (pI) of 5.8 and the other 44.8 kDa with pI 4.0, were elevated during SD to 60, 100, and 200 meters sea water (msw). The expression of these proteins returned to pre-diving level when the SD training was completed. The two proteins were identified using in-gel digestion and mass spectrometric analysis; the 32.4 kDa protein was transthyretin and the 44.8 kDa protein was alpha-1-acid glycoprotein 1. Oxidation was detected at methionine 13 of transthyretin and at methionine 129 of alpha-1-acid glycoprotein 1 by tandem mass spectrometry. Moreover, haptoglobin was up-regulated during the decompression phase of 200 msw. These plasma proteins up-regulated during SD have a common function as anti-oxidants. This suggests that by coordinating their biological effects, these proteins activate a defense mechanism to counteract the effects of hyperbaric-hyperoxic conditions during SD.

Blood Gene Expression and Vascular Function Biomarkers in Professional Saturation Diving

“…In a previous experiment, 600 mg of vitamin C, 150 mg of α-tocopherol (vitamin E) and 600 mg of tea catechins given to divers during a 400 msw deep saturation dive, every day for 40 days; prevented hepatic disturbances ( Ikeda et al, 2004 ). A recent publication demonstrated that divers’ endogenous anti-oxidant mechanisms counteracted the effects of hyperbaric hyperoxia after 200 msw saturation diving ( Domoto et al, 2016 ).…”

Evolution of the plasma proteome of divers before and after a single SCUBA dive

“…Domoto et al. recently used a precipitation step with 1:10 cold acetone . However, preliminary experiments preceding our first study on the plasma proteome of rats showed that the use of a precipitation step led to biased and non‐conclusive results and therefore, has been used neither in the first study nor in the present work, for the sake of comparison between the two studies.…”

“…Recently, Domoto et al. showed an elevation of TTR plasma abundance during saturation diving before returning to pre‐dive levels after the dive .…”

Transthyretin: From Structural Stability to Osteoarticular and Cardiovascular Diseases

“…TTR and certain plasma proteins, including hemopexin, alpha-1-antitrypsin, haptoglobin β-chain, apolipoprotein A1, and hemoglobin beta chain, were identified as candidates that can play a crucial role in adaptation to hypoxic stress due to limited oxygen availability [ 81 ]. In hyperbaric hyperoxia during saturation diving, TTR (and α-1-acid glycoprotein 1) is upregulated and oxidized (at methionine residues) [ 82 ]. The physiological response in hyperoxia includes physiological and biochemical changes to the immune system and an increase in the levels of ROS, heat shock proteins, nitric oxide, and cytokines [ 82 ].…”

“…In hyperbaric hyperoxia during saturation diving, TTR (and α-1-acid glycoprotein 1) is upregulated and oxidized (at methionine residues) [ 82 ]. The physiological response in hyperoxia includes physiological and biochemical changes to the immune system and an increase in the levels of ROS, heat shock proteins, nitric oxide, and cytokines [ 82 ].…”