Surfactin is a cyclic lipopeptide biosurfactant. Transposon mutagenesis was performed in Bacillus subtilis strain 168, and a surfactin-susceptible mutant, strain 801, was isolated. Analysis of the region of insertion revealed that yerP was the determinant of surfactin self-resistance. YerP had homology with the resistance, nodulation, and cell division (RND) family proton motive force-dependent efflux pumps only characterized in gram-negative strains. The yerP-deficient strain 802, in which the internal region of the yerP gene of B. subtilis strain 168 was deleted, showed susceptibility to acriflavine and ethidium bromide. When strain 802 was converted to a surfactin producer by introducing a functional sfp which encodes a 4-phosphopantetheinyl transferase and is mutated in B. subtilis strain 168, this yerP-deficient strain produced surfactin, although surfactin production was significantly reduced. The expression of yerP was at its maximum at the end of the logarithmic growth phase and was not induced by surfactin. yerP is the first RND-like gene characterized in gram-positive strains and is supposed to be involved in the efflux of surfactin.

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp he pulmonary hypertension that develops in hypobaric hypoxia is characterized by structural remodeling of the heart (eg, right ventricular hypertrophy). 1-7 Over the past 20 years or so, various factors and influences, including the adrenergic-receptor system, have been shown to be involved in such cardiovascular remodeling processes. [8][9][10][11][12] It is well known that hypoxia stimulates endothelial cells to release adenosine triphosphate (ATP). Purinergic P2 nucleotide receptors on endothelial cells bind this ATP, triggering secretion of nitric oxide and consequent vasodilation. The P2 class of nucleotide receptors includes the P2X receptor, which is a ligand-gated receptor channel, and the G protein-coupled P2Y receptor. 13,14 Recently, the P2X4 receptor (P2X4R) has been reported to control vascular tone and vessel remodeling in at least some blood vessels. 15-19 Interestingly, P2X4R is an important subunit of the native cardiac myocyte P2X receptor, 17 and cardiac-restricted overexpression of P2X4R can induce an enhanced contractile state of the intact heart. 20 More recently, it was found that cardiac overexpression of P2X4R increased cardiac contractility and survival in a model of myocardial infarction-induced cardiac failure. 21 It has therefore emerged as a key factor in the enhancement of cardiac performance. However, no reports have been published of alterations in P2X4R expression in certain organs, especially the heart, upon exposure to hypobaric hypoxia, and little is known about any changes in P2X4R expression in hypoxia-induced pulmonary hypertension (in which only RV is exposed to pressure overload).Even if changes in P2X4R expression occur during exposure to hypobaric hypoxia and show an apparent relation to the pulmonary pressure overload, it needs to be firmly established: (1) whether the changes in P2X4R (at both the protein and mRNA levels) occurring in certain organs, especially the heart, are coupled to the elevation in pulmonary arterial pressure seen after exposure to hypobaric hypoxia; (2) whether the changes in P2X4R protein occurring in certain organs as an adaptation to hypobaric hypoxic exposure are mirrored by similar changes at the mRNA level; and (3) whether the dis- Expression of P2X4R mRNA and Protein in RatsWith Hypobaric Hypoxia-Induced Pulmonary HypertensionYuichiro Ohata, MD; Sho Ogata, MD; Kuniaki Nakanishi, MD; Fumiko Kanazawa; Maki Uenoyama; Sadayuki Hiroi, PhD; Susumu Tominaga; Toshiaki Kawai, MD Background: The experimental pulmonary hypertension that develops in hypobaric hypoxia is characterized by structural remodeling of the heart. The P2X4 receptor (P2X4R) controls vascular tone and vessel remodeling in several blood vessels, and it has emerged as a key factor in the enhancement of cardiovascular performance.