Inorganic polyphosphates are important for cell survival and motility of human skin keratinocytes

Simbulan-Rosenthal, Cynthia M.; Gaur, Anirudh; Sanabria, Virginia A.; Dussan, Lucia J.; Saxena, Rajiv; Schmidt, J.E.; Kitani, Takashi; Chen, You-Shin; Rahim, Said; Üren, Aykut; Crooke, Elliott; Rosenthal, Dean S.

doi:10.1111/exd.12729

Cited by 17 publications

(17 citation statements)

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“…PPK levels and activity are tightly regulated, maintaining steady-state polyP concentrations in the bacterial cytosol at low micromolar levels, even in mutant strains deficient in PPX [27]. PolyP synthesis is [33]).…”

Section: Polyp In Prokaryotesmentioning

confidence: 99%

“…Inorganic Polyphosphates Are Important for Cell Survival and Motility of Human Skin… DOI: http://dx.doi.org /10.5772/intechopen.87183 upregulated during nutrient deprivation [28,29], or during osmotic [28], acidic pH [30], oxidative [31], or heat [32] stresses, potentially depleting cellular ATP pools by converting millimolar levels of ATP to long polyP chains (>1000 Pi) [31]. polyP levels are measured using enzyme-based assays that employ ppk to generate ATP from ADP, using luciferase as a reporter [33]. In another assay, cells are labeled with 32 P i ; polyP is isolated and hydrolyzed with PPX1, and thin-layer chromatography or phosphoimage analysis is performed [17].…”

Section: Polyp In Prokaryotesmentioning

confidence: 99%

“…Inorganic polyP shows promise in different phases of wound healing, including hemostasis and re-epithelialization, as polyP is a normal component of different cells that play a role in this process, including platelets, dermal fibroblasts, and keratinocytes. The use of polyP as a therapeutic for acute and chronic wounding has begun to garner interest, in part because of experiments elucidating its role in wound healing [33], as well as in hemostasis [69,[94][95][96][97][98][99]. We have recently shown a role for polyP in the response to UV survival, cell motility, and wound healing [33].…”

Section: The Contribution Of Polyp To Cell Survival Proliferation Amentioning

confidence: 99%

“…The use of polyP as a therapeutic for acute and chronic wounding has begun to garner interest, in part because of experiments elucidating its role in wound healing [33], as well as in hemostasis [69,[94][95][96][97][98][99]. We have recently shown a role for polyP in the response to UV survival, cell motility, and wound healing [33]. Addition of exogenous polyP increased the rate of wound healing in standard scratch wound assays in vitro [33].…”

Section: The Contribution Of Polyp To Cell Survival Proliferation Amentioning

confidence: 99%

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Inorganic Polyphosphates Are Important for Cell Survival and Motility of Human Skin Keratinocytes and Play a Role in Wound Healing

Simbulan-Rosenthal¹,

Carney²,

Gaur³

et al. 2020

Contemporary Topics About Phosphorus in Biology and Materials

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Inorganic polyphosphate (polyP) is a simple ancient polymer of linear chains of orthophosphate residues linked by high energy phospho-anhydride bonds ubiquitously found in all organisms. Despite its structural simplicity, it plays diverse functional roles. polyP is involved in myriad of processes including serving as microbial phosphagens, buffer against alkalis, Ca 2+ storage, metal-chelating agents, pathogen virulence, cell viability and proliferation, structural component and chemical chaperones, and in the microbial stress response. In mammalian cells, polyP has been implicated in blood coagulation, inflammation, bone differentiation, cell bioenergetics, signal transduction, Ca 2+-signaling, neuronal excitability, as a protein-stabilizing scaffold, and in wound healing, among others. This chapter will discuss (1) polyP metabolism and roles of polyP in prokaryotic and eukaryotic cells, (2) the contribution of polyP to survival, cell proliferation, and motility involved in wound healing in human skin keratinocytes, (3) the use of polyP-containing platelet-rich plasma (PRP) to promote wound healing in acute and chronic wounds, including burns, and (4) the use of polyP-containing PRP in excisional wound models to promote faster healing. While polyP shows promise as a therapeutic agent to accelerate healing for acute and chronic wounds, the molecular mechanisms as a potent modulator of the wound healing process remain to be elucidated.

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Section: Polyp In Prokaryotesmentioning

confidence: 99%

Section: Polyp In Prokaryotesmentioning

confidence: 99%

Section: The Contribution Of Polyp To Cell Survival Proliferation Amentioning

confidence: 99%

Section: The Contribution Of Polyp To Cell Survival Proliferation Amentioning

confidence: 99%

See 2 more Smart Citations

Inorganic Polyphosphates Are Important for Cell Survival and Motility of Human Skin Keratinocytes and Play a Role in Wound Healing

Simbulan-Rosenthal¹,

Carney²,

Gaur³

et al. 2020

Contemporary Topics About Phosphorus in Biology and Materials

Self Cite

View full text Add to dashboard Cite

show abstract

“…Wang et al first used this approach to study the role of polyP role in mammalian target of rapamycin (mTor) activation in MCF-7 mammary cancer cells (Wang et al, 2003). Subsequently others have used ectopic expression of Ppx1 to study the role of PolyP in mitochondria (Abramov et al, 2007;Seidlmayer et al, 2012), wound healing (Simbulan-Rosenthal et al, 2015), the DNA damage response (Bru et al, 2017), and glycolysis (Nakamura et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

A broad response to intracellular long-chain polyphosphate in human cells

Bondy‐Chorney

Abramchuk

Nasser

et al. 2020

Preprint

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Polyphosphates (PolyP) are composed of long chains of inorganic phosphates linked together by phosphoanhydride bonds. They are found in all kingdoms of life, playing roles in cell growth, infection, and blood coagulation. A resurgence in interest in polyP has shown links to diverse aspects of human disease. However, unlike in bacteria and lower eukaryotes, the mammalian enzymes responsible for polyP metabolism are not known. Many studies have resorted to adding polyP to cell culture media, but it is not clear if externally applied polyP enters the cell to impact signaling events or whether their effect is mediated exclusively by extracellular receptors. For the first time, we use RNA-seq and mass spectrometry to define a broad impact of polyP produced inside of mammalian cells via ectopic expression of the E. coli polyP synthetase Ppk1. RNA-seq demonstrates that Ppk1 expression impacts expression of over 350 genes enriched for processes related to transcription and cell motility. Analysis of proteins via label-free mass spectrometry identified over 100 changes with functional enrichment in cell migration. Follow up work suggests a role for internally-synthesized polyP in promoting activation of mTOR and ERK1/2-EGR1 signaling pathways implicated in cell growth and stress. Finally, fractionation analysis shows that polyP accumulated in multiple cellular compartments and was associated with the relocalization several nuclear/cytoskeleton proteins, including chromatin bound proteins DEK, TAF10, GTF2I and translation initiation factor eIF5b. Our work is the first to demonstrate that internally produced polyP can activate diverse signaling pathways in human cells.Significance StatementFor many years following its discovery in 1890, polyphosphates (polyP) were dismissed as evolutionary fossils. Best understood for its role in bacteria and yeast, our understanding of polyP in mammals remains rudimentary because the enzymes that synthesize and degrade polyP in mammalian systems are currently unknown. In our work, we carried out large-scale transcriptome and proteome approaches on human cells designed to accumulate internally produced polyP via ectopic expression of a bacterial polyP synthetase. Our work is the first to systematically assess the impact of increased intracellular polyP.

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The dynamic relationship between inorganic polyphosphate and adenosine triphosphate in human non‐small cell lung cancer H1299 cells

Tsutsumi,

Tippayamontri,

Hayashi

et al. 2024

FEBS Open Bio

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Inorganic polyphosphate (polyP) plays a vital role in cellular energy metabolism and signaling, owing to its structure and high‐energy phosphate bonds. Intracellular ATP functions both as a cellular energy source and a key factor in cell death, and ATP dynamics in tumor cells are crucial for advancing cancer therapy. In this study, we explored the interplay between polyP and ATP in cellular energy metabolism. Treatment with polyP did not affect cell proliferation of human non‐small cell lung cancer H1299 and human glioblastoma T98G cell lines as compared to their respective control cells until 72 h post‐treatment. The mitochondrial membrane potential (MMP) in polyP‐treated cells was low, contrasting with the time‐dependent increase observed in control cells. While the ATP content increased over time in untreated and Na‐phosphate‐treated control cells, it remained unchanged in polyP‐treated cells. Furthermore, the addition of cyclosporine A, a mitochondrial permeability transition pore (mPTP) inhibitor, failed to restore ATP levels in polyP‐treated cells. We performed lactate assays and western blot analysis to evaluate the effect of polyP on glucose metabolism and found no significant differences in lactate secretion or glucose‐6‐phosphate dehydrogenase (G6PD) activity between polyP‐treated and control cells. Additional pyruvate restored MMP but had no effect on the cellular ATP content in polyP‐treated cells. We observed no correlation between the Warburg effect and glucose metabolism during ATP depletion in polyP‐treated cells. Further investigation is warranted to explore the roles of polyP and ATP in cancer cell energy metabolism, which might offer potential avenues for therapeutic interventions.

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Inorganic polyphosphates are important for cell survival and motility of human skin keratinocytes

Cited by 17 publications

References 9 publications

Inorganic Polyphosphates Are Important for Cell Survival and Motility of Human Skin Keratinocytes and Play a Role in Wound Healing

Inorganic Polyphosphates Are Important for Cell Survival and Motility of Human Skin Keratinocytes and Play a Role in Wound Healing

A broad response to intracellular long-chain polyphosphate in human cells

The dynamic relationship between inorganic polyphosphate and adenosine triphosphate in human non‐small cell lung cancer H1299 cells

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