Signalling Properties of Inositol Polyphosphates

Maffucci, Tania; Falasca, Marco

doi:10.3390/molecules25225281

Cited by 14 publications

(9 citation statements)

References 82 publications

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“…In addition, InsPs are a group of metabolites in all eukaryotes, critical for gene expression, protein stabilization, and calcium transport. [42,43] InsPs pathways were upregulated after the LPS challenge in WT and Hmgb1 ΔMye neutrophils. Notably, neutrophils from Hmgb1 ΔMye mice showed significant downregulation of multiple pathways involved in InsPs biosynthesis and metabolism at baseline.…”

Section: Discussionmentioning

confidence: 94%

Deficiency of neutrophil high-mobility group box-1 in liver transplant recipients exacerbates early allograft injury in mice

Song

Han

et al. 2023

Hepatology

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Background and Aims: Early allograft dysfunction (EAD) is a severe event leading to graft failure after liver transplant (LT). Extracellular high-mobility group box-1 (HMGB1) is a damage-associated molecular pattern that contributes to hepatic ischemia-reperfusion injury (IRI). However, the contribution of intracellular HMGB1 to LT graft injury remains elusive. We hypothesized that intracellular neutrophil-derived HMGB1 from recipients protects from post-LT EAD. Approach and Results: We generated mice with conditional ablation or overexpression of Hmgb1 in hepatocytes, myeloid cells, or both. We performed LTs and injected lipopolysaccharide (LPS) to evaluate the effect of intracellular HMGB1 in EAD. Ablation of Hmgb1 in hepatocytes and myeloid cells of donors and recipients exacerbated early allograft injury after LT. Ablation of Hmgb1 from liver grafts did not affect graft injury; however, lack of Hmgb1 from recipient myeloid cells increased reactive oxygen species (ROS) and inflammation in liver grafts and exacerbated injury. Neutrophils lacking HMGB1 were more activated, showed enhanced pro-oxidant and pro-inflammatory signatures, and reduced biosynthesis and metabolism of inositol polyphosphates (InsPs). On LT reperfusion or LPS treatment, there was significant neutrophil mobilization and infiltration into the liver and enhanced production of ROS and pro-inflammatory cytokines when intracellular Hmgb1 was absent. Depletion of neutrophils using anti-Ly6G antibody attenuated graft injury in recipients with myeloid cell Hmgb1 ablation. Conclusions: Neutrophil HMGB1 derived from recipients is central to regulate their activation, limits the production of ROS and pro-inflammatory cytokines, and protects from early liver allograft injury.

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Section: Discussionmentioning

confidence: 94%

Deficiency of neutrophil high-mobility group box-1 in liver transplant recipients exacerbates early allograft injury in mice

Song

Han

et al. 2023

Hepatology

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“…Decreased inositol levels in lung cancer and cerebral astrocytoma have been observed. Accordingly, exogenous inositol (myo-inositol or IP6) can inhibit cancer cell growth (44)(45)(46). It is unknown if the patients in this study were exposed to this compound or its derivatives.…”

Section: Discussionmentioning

confidence: 97%

Metabolic Alterations in Sputum and Exhaled Breath Condensate of Early Stage Non-Small Cell Lung Cancer Patients After Surgical Resection: A Pilot Study

et al. 2022

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Every year, close to two million people world-wide are diagnosed with and die of lung cancer. Most patients present with advanced-stage cancer with limited curative options and poor prognosis. Diagnosis of lung cancer at an early stage provides the best chance for a cure. Low- dose CT screening of the chest in the high-risk population is the current standard of care for early detection of lung cancer. However, CT screening is invasive due to radiation exposure and carries the risk of unnecessary biopsies in non-cancerous tumors. In this pilot study, we present metabolic alterations observed in sputum and breath condensate of the same population of early- stage non-small cell lung cancer (NSCLC) patients cancer before and after surgical resection (SR), which could serve as noninvasive diagnostic tool. Exhaled breath condensate (EBC) (n=35) and sputum (n=15) were collected from early-stage non-small cell lung cancer (NSCLC) patients before and after SR. Median number of days for EBC and sputum collection before and after SR were 7 and 42; and 7 and 36 respectively Nuclear magnetic resonance (NMR) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) were used to analyze the metabolic profile of the collected samples. A total of 26 metabolites with significant alteration post SR were identified, of which 14 (54%) were lipids and 12 constituted nine different chemical metabolite classes. Eighteen metabolites (69%) were significantly upregulated and 8 (31%) were downregulated. Median fold change for all the up- and downregulated metabolites (LC-QTOF-MS) were 10 and 8, respectively. Median fold change (MFC) in concentration of all the up- and downregulated metabolites (NMR) were 0.04 and 0.27, respectively. Furthermore, glucose (median fold change, 0.01, p=0.037), adenosine monophosphate (13 log fold, p=0.0037) and N1, N12- diacetylspermine (8 log fold p=0.011) sputum levels were significantly increased post-SR. These identified sputa and EBC indices of altered metabolism could serve as basis for further exploration of biomarkers for early detection of lung cancer, treatment response, and targets for drug discovery. Validation of these promising results by larger clinical studies is warranted.

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“…Phytates in plants represent a source of energy and antioxidant capacity (as a phosphate groups donor), but they have a predominant role as storage mineral chelating agents (depot of Cu 2+ and Zn 2+ cations in particular) due to the presence of negative charges at physiological pH (Barrientos and Murthy, 1996;Persson et al, 1998;Raboy, 2003). In addition, this compound is present outside the plant kingdom and can be found in all organisms (excluding prokaryotes), where, together with its derivatives, it is involved in cell metabolism, homeostasis, and pathological conditions (Bohn et al, 2008;Maffucci and Falasca, 2020;Silva et al, 2021). Phytates were first discovered in 1855 by a German researcher Theodor Hartig who identified circular particles in different plant seeds (Hartig, 1855;Khoo and Wolf, 1970).…”

Section: Introductionmentioning

confidence: 99%

Phytates as a natural source for health promotion: A critical evaluation of clinical trials

et al. 2023

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Phytates are a type of organophosphorus compound produced in terrestrial ecosystems by plants. In plant feeds, phytic acid and its salt form, phytate, account for 60%–80% of total phosphorus. Because phytate is a polyanionic molecule, it can chelate positively charged cations such as calcium, iron, and zinc. Due to its prevalence in vegetal tissues and the fact that people consume plants, phytate was first considered a potential health benefit. This updated review aims to summarize the current data on the results of clinical trials of phytates on human health, highlighting both beneficial and undesirable effects. To obtain these updated data, published papers in electronic databases such as PubMed/MedLine, TRIP database, Wiley, Google Scholar, Baidu, and Scopus were searched. Study results have shown that phytate can have beneficial health effects such as antioxidant, anticancer potential and reduction of pathological calcifications in blood vessels and organs; but also, negative effects by reducing the absorption of minerals important for maintaining the homeostasis of the human body. According to these recent results derived from recent clinical studies, phytates may be a potential natural source for health benefits. To improve clinical efficacy and human health benefits, further dose-response studies are needed to determine effective therapeutic doses and potential interactions with conventional drugs.

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Signalling Properties of Inositol Polyphosphates

Cited by 14 publications

References 82 publications

Deficiency of neutrophil high-mobility group box-1 in liver transplant recipients exacerbates early allograft injury in mice

Deficiency of neutrophil high-mobility group box-1 in liver transplant recipients exacerbates early allograft injury in mice

Metabolic Alterations in Sputum and Exhaled Breath Condensate of Early Stage Non-Small Cell Lung Cancer Patients After Surgical Resection: A Pilot Study

Phytates as a natural source for health promotion: A critical evaluation of clinical trials

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