Incorporation of [32P]orthophosphate into long chains of inorganic polyphosphate within lysosomes of human fibroblasts.

Pisoni, Ronald L.; Lindley, E R

doi:10.1016/s0021-9258(19)50570-1

Cited by 75 publications

(11 citation statements)

References 30 publications

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“…PolyP accumulated in cell organelles including mitochondria, vesicle‐like structures and nucleus in chondrocytes. This is similar to what occurs in other cell types 6,8,41‐43 . It is not clear why and how this cytoplasmic redistribution occurs, but polyP seems to follow calcium and its cytosolic distribution.…”

Section: Discussionsupporting

confidence: 67%

The anabolic effect of inorganic polyphosphate on chondrocytes is mediated by calcium signalling

Gawri

Bielecki

Salter

et al. 2021

Journal Orthopaedic Research

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Inorganic polyphosphates (polyP) are polymers composed of phosphate residues linked by energy‐rich phosphoanhydride bonds. As polyP can bind calcium, the hypothesis of this study is that polyP enters chondrocytes and exerts its anabolic effect by calcium influx through calcium channels. PolyP treatment of cartilage tissue formed in 3D culture by bovine chondrocytes showed an increase in proteoglycan accumulation but only when calcium was also present at a concentration of 1.5 mM. This anabolic effect could be prevented by treatment with either ethylene glycol‐bis(β‐aminoethyl ether)‐N,N,N',N'‐tetraacetic acid or the calcium channel inhibitors gadolinium and nifedipine. Calcium and polyP cotreatment of chondrocytes in monolayer culture resulted in calcium oscillations that were polyP chain length specific and were inhibited by gadolinium and nifedipine. The calcium influx resulted in increased gene expression of sox9, collagen type II, and aggrecan which was prevented by treatment with either calphostin, an inhibitor of protein kinase C, and W7, an inhibitor of calmodulin; suggesting activation of the protein kinase C‐calmodulin pathway. Tracing studies using 4′,6‐diamidino‐2‐phenylindole, Mitotracker Red, and/or Fura‐AM staining showed that polyP was detected in the nucleus, mitochondria, and intracellular vacuoles suggesting that polyP may also enter the cell. PolyP colocalizes with calcium in mitochondria. This study demonstrates that polyP requires the influx of calcium to regulate chondrocyte matrix production, likely via activating calcium signaling. These findings identify the mechanism regulating the anabolic effect of polyP in chondrocytes which will help in its clinical translation into a therapeutic agent for cartilage repair.

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Section: Discussionsupporting

confidence: 67%

The anabolic effect of inorganic polyphosphate on chondrocytes is mediated by calcium signalling

Gawri

Bielecki

Salter

et al. 2021

Journal Orthopaedic Research

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“…Also in other body fluids, like in synovial fluids, polyP exists . Within mammalian cells, this polymer has been identified in lysosomes, dense granules of the acidocalcisomes, mitochondria, and nuclei …”

Section: Physiological Roles Of Polypmentioning

confidence: 99%

Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix

2019

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Inorganic polyphosphates (polyP) consist of linear chains of orthophosphate residues, linked by high-energy phosphoanhydride bonds. They are evolutionarily old biopolymers that are present from bacteria to man. No other molecule concentrates as much (bio)chemically usable energy as polyP. However, the function and metabolism of this long-neglected polymer are scarcely known, especially in higher eukaryotes. In recent years, interest in polyP experienced a renaissance, beginning with the discovery of polyP as phosphate source in bone mineralization. Later, two discoveries placed polyP into the focus of regenerative medicine applications. First, polyP shows morphogenetic activity, i.e., induces cell differentiation via gene induction, and, second, acts as an energy storage and donor in the extracellular space. Studies on acidocalcisomes and mitochondria provided first insights into the enzymatic basis of eukaryotic polyP formation. In addition, a concerted action of alkaline phosphatase and adenylate kinase proved crucial for ADP/ATP generation from polyP. PolyP added extracellularly to mammalian cells resulted in a 3-fold increase of ATP. The importance and mechanism of this phosphotransfer reaction for energy-consuming processes in the extracellular matrix are discussed. This review aims to give a critical overview about the formation and function of this unique polymer that is capable of storing (bio)chemically useful energy.

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“…Short chains (60-100 phosphates) have been reported in human platelets (M€ uller et al, 2009;Ruiz et al, 2004). The longest chains have been reported in specific cell and tissue types, such as the lysosomes of human fibroblasts (100-600 phosphates) (Pisoni and Lindley, 1992), the rodent brain, and cell lines such as HEK293, where chains were found to predominantly be 800 phosphates long (Kumble and Kornberg, 1995). Furthermore, endogenous polyP chains in PC3 cells were shown to be predominantly R650 phosphates (Nickel et al, 2015).…”

Section: Discussionmentioning

confidence: 97%

“…PolyP chains synthesized by PPK in mammalian cells are of the long-chain type (>700 phosphate moieties), similar to the polyP synthesized by E. coli under stress conditions. A wide range of sizes of polyP chains (from 2 to >5,000 phosphates in length) have been reported in mammalian tissues and cells (Gabel and Thomas, 1971;Kumble and Kornberg, 1995;Pisoni and Lindley, 1992). Short chains (60-100 phosphates) have been reported in human platelets (M€ uller et al, 2009;Ruiz et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

A Broad Response to Intracellular Long-Chain Polyphosphate in Human Cells

et al. 2020

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Incorporation of [32P]orthophosphate into long chains of inorganic polyphosphate within lysosomes of human fibroblasts.

Cited by 75 publications

References 30 publications

The anabolic effect of inorganic polyphosphate on chondrocytes is mediated by calcium signalling

The anabolic effect of inorganic polyphosphate on chondrocytes is mediated by calcium signalling

Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix

A Broad Response to Intracellular Long-Chain Polyphosphate in Human Cells

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