Gen activates Nrf2 [36, 817] and its downstream heme oxygenase-1 (HO-1) [36, 51, 52, 65, 71, 81, 82, 843]. Kawamura and colleagues reported that hydrogen did not mitigate hyperoxic lung injury in Nrf2knockout mice [82]. Similarly, Ohsawa and colleagues reported that hydrogen enhanced mitochondrial functions and induced nuclear translocation of Nrf2 at the Symposium of Medical Molecular Hydrogen in 2012 and 2013. They proposed that hydrogen induces an adaptive response against oxidative strain, which is also known as a hormesis impact. These studies indicate that the effectof hydrogen is mediated by Nrf2, however the mechanisms of how Nrf2 is activated by hydrogen stay to become solved. A further interesting mechanism is that hydrogen modulates miRNA expressions [64, 94]. Hydrogen regulates expressions of miR-9, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21300292 miR-21, and miR-199, and modifies expressions of IKK-, NF-B, and PDCD4 in LPSactivated retinal microglia cells [64]. Similarly, evaluation of miRNA profiles of hippocampal neurons for the duration of IR injury revealed that hydrogen inhibits IR-induced expression with the miR-200 family members by minimizing ROS production, which has led to suppression of cell death [94]. Nonetheless, modulation of miRNA expression can not solely explain all of the biological effects mediated by hydrogen. Also, mechanisms underlying modulated miRNA expressions remain to become elucidated. Leukadherin-1 site Matsumoto and colleagues reported that oral intake of hydrogen water elevated gastric expression and secretion of ghrelin and that the neuroprotective effect of hydrogen water was abolished by the ghrelin receptorantagonist and by the ghrelin secretion-antagonist [95]. As stated above, we’ve shown that hydrogen water, but not hydrogen gas, prevented development of Parkinson’s disease in a rat model [11]. Prominent impact of oral hydrogen intake rather than hydrogen gas inhalation can be partly accounted for by gastric induction of ghrelin. Recently, Ohta and colleagues showed in the 5th Symposium of Medical Molecular Hydrogen at Nagoya, Japan in 2015 that hydrogen influences a free of charge radical chain reaction of unsaturated fatty acid on cell membrane and modifies its lipid peroxidation procedure. Furthermore, they demonstrated that air-oxidized phospholipid that was made either in the presence or absence of hydrogen in vitro, offers rise to diverse intracellular signaling and gene expression profiles when added towards the culture medium. They also showed that this aberrant oxidization of phospholipid was observed having a low concentration of hydrogen (at the very least 1.3 ), suggesting that the biological effects of hydrogen could possibly be explained by the aberrant oxidation of phospholipid beneath hydrogen exposure. Among the several molecules that are altered by hydrogen, most are predicted to become passengers (downstream regulators) which can be modulated secondarily to a transform in a driver (master regulator). The most effective way to determine the master regulator is to prove the effect of hydrogen in an in vitro program. Though, to our understanding, the study on lipid peroxidation has not yet been published, the cost-free radical chain reaction for lipid peroxidation may be the second master regulator of hydrogen subsequent towards the radical scavenging impact. We are also analyzing other novel molecules as you can master regulators of hydrogen (in preparation). Taken together, hydrogen is likely to have various master regulators, which drive a diverse array of downstreamIchihara et al. Health-related Gas Research (2015) 5:Page five ofTable 2 Disease model.
