Inositol 1,2,3-trisphosphate and inositol 1,2- and/or 2,3-bisphosphate are normal constituents of mammalian cells

Abstract

1. An inositol trisphosphate (InsP3) distinct from Ins(1,4,5)P3 and Ins(1,3,4)P3, which we previously observed in myeloid and lymphoid cells [French, Bunce, Stephens, Lord, McConnell, Brown, Creba and Michell (1991) Proc R. Soc. London B 245, 193-201; Bunce, French, Allen, Mountford, Moore, Greaves, Michell and Brown (1993) Biochem. J. 289, 667-673], is present in WRK1 rat mammary tumour cells and pancreatic endocrine beta-cells. 2. It has been identified as Ins(1,2,3)P3 by a combination of oxidation to ribitol, a structurally diagnostic polyol, and ammoniacal hydrolysis to identified inositol monophosphates. 3. Ins(1,2,3)P3 concentration in HL60 cells changed little during stimulation by ATP or fMetLeuPhe or during neutrophilic or monocytic differentiation, and Ins(1,2,3)P3 was unresponsive to vasopressin in WRK1 cells. 4. Ins(1,2,3)P3 was usually more abundant than Ins(1,4,5)P3, often being present at concentrations between approximately 1 microM and approximately 10 microM. 5. HL60, WRK-1 and lymphoid cells also contain Ins(1,2)P2 or Ins(2,3)P2, or a mixture of these two enantiomers, as a major InsP2 species. 6. Ins(1,2,3)P3 and Ins(1,2)P2/Ins(2,3)P2 are readily detected in cells labelled for long periods, but not in acutely labelled cells. This behaviour resembles that of InsP6, the most abundant cellular inositol polyphosphate that includes the 1,2,3-trisphosphate motif, which also achieves isotopic equilibrium with inositol only slowly. 7. Ins(1,2,3)P3 is the major InsP3 that accumulates during metabolism of InsP6 by WRK-1 cell homogenates. 8. Possible metabolic relationships between Ins(1,2,3)P3, Ins(1,2)P2/Ins(2,3)P2 and other inositol polyphosphates in cells, and a possible role for Ins(1,2,3)P3 in cellular iron handling, are considered.

New Horizons in Cellular Regulation by Inositol Polyphosphates: Insights from the Pancreaticβ-Cell

“…We should clarify that the importance of InsP 6 stems both from its own role and as a platform from which other regulatory molecules are derived. Examples of the latter include the inositol pyrophosphates (Barker et al, 2009b;Shears et al, 2011;Saiardi, 2012) (see section IV) or the Ins(1,2,3)P 3 -based inositol polyphosphates with iron-binding properties (Barker et al, 1995;Spiers et al, 1996;Irvine, 2005). In terms of the direct effects of the molecule, two or three different modes of operation for InsP 6 can be identified.…”

“…However, it still may fulfill this role in other cellular contexts in vesicles or other subcellular organelles and more widely in nutrition, in which its abundance and chelating properties are known to cause malnutrition in developing countries (Zhou and Erdman, 1995). Furthermore, the InsP 6 breakdown product Ins(1,2,3)P 3 (Barker et al, 1995) has now been subject to the same rigorous assessment as InsP 6 (Veiga et al, 2009) but, in contrast, remains one of the best candidates in the mammalian cell for both complexing iron and preventing iron-catalyzed free radical cascades, acting therefore as a potent antioxidant. The importance of InsP 6 as an antioxidant then becomes as the reservoir from which Ins(1,2,3)P 3 is derived.…”

Metabolic Relations of Inositol 3,4,5,6-Tetrakisphosphate Revealed by Cell Permeabilization. Identification of Inositol 3,4,5,6-Tetrakisphosphate 1-Kinase and Inositol 3,4,5,6-Tetrakisphosphate Phosphatase Activities in Mesophyll Cells

“…None of the isomers detected is unique to plants though d/l-Ins(2,4,5) P 3 and Ins(1,2,3) P 3 have only occasionally been reported in vivo in any kingdom Hanke, 1992, 1996b;Barker et al, 1995). Although Ins(1,4,5) P 3 is one of only a few InsP 3 s identified to date, it appears that this isomer is only a minor component of the inositol phosphate complement of higher plants.…”

“…It occurs in non-highly differentiated cells (mesophyll cells) in the fronds and turions of S. polyrhiza, in root cortex cells of Arabidopsis, and in terminally differentiated cells in barley aleurone. It is likely that the route of Ins(1,2,3) P 3 generation is shared in monocots and dicots and perhaps also in animal cells (Barker et al, 1995), where it has been shown that Ins(1,2,3) P 3 is a product of InsP 6 breakdown by cell homogenates. Clearly, Ins(1,2,3) P 3 is not restricted to specialized cells or storage tissues in plants, so we should consider a general "housekeeping" function for this isomer.…”

“…Clearly, Ins(1,2,3) P 3 is not restricted to specialized cells or storage tissues in plants, so we should consider a general "housekeeping" function for this isomer. One such suggestion is that Ins(1,2,3) P 3 is an inhibitor of hydroxyl free radical formation (Barker et al, 1995;Phillippy and Graf, 1997).…”