Hypoxanthine causes endothelial dysfunction through oxidative stress-induced apoptosis

Kim, You-Jin; Ryu, Hye‐Myung; Choi, Jiyoung; Cho, Jang‐Hee; Kim, Chan‐Duck; Park, Sun-Hee; Kim, Yong-Lim

doi:10.1016/j.bbrc.2016.11.119

Cited by 62 publications

(41 citation statements)

References 19 publications

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“…In humans, it has been studied in the context of diseases, such as gout, Lesch-Nyhan disease, and endothelial cell injury of cardiovascular diseases. Although these conditions have different etiologies and clinical evolution, they have in common an excessive accumulation of hypoxanthine and uric acid, whose catabolism leads to oxidative-stress-induced apoptosis (42)(43)(44). In bacteria, hypoxanthine has been mainly studied in relation to DNA damage and mutagenesis due to spontaneous deamination of adenine, which yields hypoxanthine and leads to AT-to-GC transitions after DNA replication (45).…”

Section: Discussionmentioning

confidence: 99%

“…Based on these results, we suggest that hypoxanthine induces the formation of wrinkles in colony biofilms of B. subtilis not by inducing the expression of biofilm-related genes, but rather by metabolic effects derived from the excess of available hypoxanthine. In this regard, we note that an excess of hypoxanthine can cause oxidative stress and cell death in eukaryotic cells by increasing the formation of reactive oxygen species when hypoxanthine is metabolized to urate (42,43). A similar catabolic pathway could be followed by hypoxanthine in B. subtilis, which possesses multiple hypoxanthine/xanthine oxidases known as PucA, PucB, PucC, PucD, and PucE (see SubtiWiki Pathways [http://subtiwiki.uni-goettingen.de/v3/pathway/ view/41]) (39).…”

Section: Discussionmentioning

confidence: 99%

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Lysinibacillus fusiformis M5 Induces Increased Complexity in Bacillus subtilis 168 Colony Biofilms via Hypoxanthine

et al. 2017

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In recent years, biofilms have become a central subject of research in the fields of microbiology, medicine, agriculture, and systems biology, among others. The sociomicrobiology of multispecies biofilms, however, is still poorly understood. Here, we report a screening system that allowed us to identify soil bacteria which induce architectural changes in biofilm colonies when cocultured with We identified the soil bacterium M5 as an inducer of wrinkle formation in colonies mediated by a diffusible signaling molecule. This compound was isolated by bioassay-guided chromatographic fractionation. The elicitor was identified to be the purine hypoxanthine using mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. We show that the induction of wrinkle formation by hypoxanthine is not dependent on signal recognition by the histidine kinases KinA, KinB, KinC, and KinD, which are generally involved in phosphorylation of the master regulator Spo0A. Likewise, we show that hypoxanthine signaling does not induce the expression of biofilm matrix-related operons and Finally, we demonstrate that the purine permease PbuO, but not PbuG, is necessary for hypoxanthine to induce an increase in wrinkle formation of biofilm colonies. Our results suggest that hypoxanthine-stimulated wrinkle development is not due to a direct induction of biofilm-related gene expression but rather is caused by the excess of hypoxanthine within cells, which may lead to cell stress and death. Biofilms are a bacterial lifestyle with high relevance regarding diverse human activities. Biofilms can be beneficial, for instance, in crop protection. In nature, biofilms are commonly found as multispecies communities displaying complex social behaviors and characteristics. The study of interspecies interactions will thus lead to a better understanding and use of biofilms as they occur outside laboratory conditions. Here, we present a screening method suitable for the identification of multispecies interactions and showcase as a soil bacterium that is able to live alongside and modify the architecture of its biofilms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lysinibacillus fusiformis M5 Induces Increased Complexity in Bacillus subtilis 168 Colony Biofilms via Hypoxanthine

et al. 2017

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“…Based on these results, we suggest that hypoxanthine induces the formation of wrinkles in colony biofilms of B. subtilis not by inducing the expression of biofilm-related genes, but rather by metabolic effects derived from the excess of available hypoxanthine. In this regard, we note that an excess of hypoxanthine can cause oxidative stress and cell death in eukaryotic cells by increasing the formation of reactive oxygen species when hypoxanthine is metabolized to urate (42,43). A similar catabolic pathway could be followed by hypoxanthine in B. subtilis, which possesses multiple hypoxanthine/xanthine oxidases known as PucA, B, C, D and E (see SubtiWiki Pathways: http://www.subtiwiki.uni-goettingen.de/apps/pathway.php?pathway=41) (39).…”

Section: Discussionmentioning

confidence: 99%

Lysinibacillus fusiformisM5 induces increased complexity inBacillus subtilis168 colony biofilms via hypoxanthine

Gallegos‐Monterrosa

Kankel

Goetze

et al. 2017

Preprint

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In recent years, biofilms have become a central subject of research in the fields of microbiology, medicine, agriculture, or systems biology amongst others. The sociomicrobiology of multispecies biofilms, however, is still poorly understood. Here, we report a screening system that allowed us to identify soil bacteria, which induce architectural changes in biofilm colonies when cocultured with B. subtilis. We identified the soil bacterium Lysinibacillus fusiformis M5 as inducer of wrinkle-formation in B.subtilis colonies mediated by a diffusible signaling molecule. This compound was isolated by bioassay-guided chromatographic fractionation. The elicitor was identified to be the purine hypoxanthine using mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. We show that the induction of wrinkle formation by hypoxanthine is not dependent on signal recognition by the histidine kinases KinA, KinB, KinC, and KinD, which are generally involved in phosphorylation of the master regulator Spo0A.Likewise, we show that hypoxanthine signaling does not induce the expression of biofilm-matrix related operons epsA-O and tasA-sipW-tapA. Finally, we demonstrate that the purine permease PbuO, but not PbuG, is necessary for hypoxanthine to induce an increase in wrinkle formation of B. subtilis biofilm colonies. Our results suggest that hypoxanthine-stimulated wrinkle development is not due to a direct induction of biofilmrelated gene expression, but rather caused by the excess of hypoxanthine within B. subtilis cells, which may lead to cell stress and death.

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“…Serum levels of this enzyme are increased in various pathological states, such as inflammatory diseases, carcinogenesis, chronic renal disease and aging (3). Furthermore, increased extracellular concentration of hypoxanthine, by the activity of xanthine oxidase also induced endothelial dysfunction and cell death (4). Recent studies suggested that endothelial dysfunction could develop due to excessive uric acid production by impairing nitric oxide production, inducing antiproliferative effects on endothelial cells, and induction of the renin-angiotensin system (5).…”

Section: Introductionmentioning

confidence: 99%

Renoprotective impact of allopurinol in elderly patients with hypertension

Mottaghi¹

2017

J Nephropathol

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Implication for health policy/practice/research/medical education:Hypertension and hyperuricemia are common problems in elderly patients. These problems could be accelerated decrease in glomerular filtration rate (GFR) with aging. It is suggested that lowering uric acid with allopurinol could be beneficial to prevent chronic insufficiency in the elderly patients with hypertension. Please cite this paper as: Mottaghi P. Renoprotective impact of allopurinol in elderly patients with hypertension.

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Hypoxanthine causes endothelial dysfunction through oxidative stress-induced apoptosis

Cited by 62 publications

References 19 publications

Lysinibacillus fusiformis M5 Induces Increased Complexity in Bacillus subtilis 168 Colony Biofilms via Hypoxanthine

Lysinibacillus fusiformis M5 Induces Increased Complexity in Bacillus subtilis 168 Colony Biofilms via Hypoxanthine

Lysinibacillus fusiformisM5 induces increased complexity inBacillus subtilis168 colony biofilms via hypoxanthine

Renoprotective impact of allopurinol in elderly patients with hypertension

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