Bacteria such as Escherichia coli must coordinate cell elongation and cell division. Elongation is regulated by an elongasome complex containing MreB actin and the transmembrane protein RodZ, which regulates assembly of MreB, whereas division is regulated by a divisome complex containing FtsZ tubulin. These complexes were previously thought to function separately. However, MreB has been shown to directly interact with FtsZ to switch to cell division from cell elongation, indicating that these complexes collaborate to regulate both processes. Here, we investigated the role of RodZ in the regulation of cell division. RodZ localized to the division site in an FtsZ-dependent manner. We also found that division-site localization of MreB was dependent on RodZ. Formation of a Z ring was delayed by deletion of rodZ , suggesting that division-site localization of RodZ facilitated the formation or stabilization of the Z ring during early cell division. Thus, RodZ functions to regulate MreB assembly during cell elongation and facilitates the formation of the Z ring during cell division in E. coli .

Molecular hydrogen (H), as a new medical gas, has protective effects in neurological disorders including Parkinson's disease (PD). In our previous report, the neuroprotective effect of drinking water with saturated H (H water) in PD mice might be due to stomach-brain interaction via release of gastric hormone, ghrelin. In the present study, we assessed the effect of H-induced ghrelin more precisely. To confirm the contribution of ghrelin in H water-drinking PD model mice, ghrelin-knock out (KO) mice were used. Despite the speculation, the effect of H water was still observed in ghrelin-KO PD model mice. To further check the involvement of ghrelin, possible contribution of ghrelin-induced vagal afferent effect was tested by performing subdiaphragmatic vagotomy before treating with H water and administration of MPTP (1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine). The protective effect of H water was still observed in the vagotomized mice in substantia nigra, suggesting that stimulation of vagal afferent nerves is not involved in H-induced neuroprotection. Other neuroprotective substitutes in ghrelin-KO mice were speculated because H-induced neuroprotection was not cancelled by ghrelin receptor antagonist, D-Lys GHRP-6, in ghrelin-KO PD model mice, unlike in wild-type PD model mice. Our results indicate that ghrelin may not be the only factor for H-induced neuroprotection and other factors can substitute the role of ghrelin when ghrelin is absent, raising intriguing options of research for H-responsive factors.

Molecular hydrogen (H2) showed protection against various kinds of oxidative-stress-related diseases. First, it was reported that the mechanism of therapeutic effects of H2 was antioxidative effect due to inhibition of the most cytotoxic reactive oxygen species, hydroxy radical (•OH). However, after chronic administration of H2 in drinking water, oxidative-stress-induced nerve injury is significantly attenuated even in the absence of H2. It suggests indirect signaling of H2 and gastrointestinal tract is involved. Indirect effects of H2 could be tested by giving H2 water only before nerve injury, as preconditioning. For example, preconditioning of H2 for certain a period (∼7 days) in Parkinson’s disease model mice shows significant neuroprotection. As the mechanism of indirect effect, H2 in drinking water induces ghrelin production and release from the stomach via β1-adrenergic receptor stimulation. Released ghrelin circulates in the body, being transported across the blood–brain barrier, activates its receptor, growth-hormone secretagogue receptor. H2-induced upregulation of ghrelin mRNA is also shown in ghrelin-producing cell line, SG-1. These observations help with understanding the chronic effects of H2 and raise intriguing preventive and therapeutic options using H2.