Changes in cellular levels of inositol polyphosphates during apoptosis

Abstract

Accumulations of higher inositol polyphosphates, diphosphoinositol polyphosphates or pyrophosphates, have been implicated to mediate cellular apoptosis. Whether cellular levels of lower inositol phosphates (lower than inositol hexakisphosphates) change during apoptosis is not known, although these inositol phosphates are known to play crucial roles in a number of cellular signaling processes including calcium mobilization. Therefore, in this study, we have examined changes in cellular levels of inositol phosphates following metabolic labeling of these compounds by [(3)H]myo-inositol and induction of apoptosis. The levels of inositol mono- and bis-phosphates were increased, whereas the levels of inositol tris- and tetrakis-phosphates decreased significantly with an increasing rate of apoptosis induced by etoposide in a dose-dependent manner. NaF treatment, which increased the rate of apoptosis in a time- and dose-dependent manner, also increased the levels of inositol mono- and bis-phosphates and drastically reduced the levels of inositol tris- and tetrakis-phosphates. Prior treatment with antimycin A, a strategy used to reverse the NaF-induced accumulations of higher InsPs, partially reduced the effects of NaF on apoptosis as well as the levels of lower InsPs. Taken together, our results suggest that cellular levels of lower InsPs are altered during apoptosis.

Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for Minpp1 in cellular stress response

“…Recent studies from various laboratories including data published from our laboratory (Agarwal et al 2010;Agarwal et al 2009) have demonstrated a close association between cytosolic concentrations of InsPs and cell death induction by apoptosis. Further studies from other laboratories have shown that lower concentrations of InsP 6 promoted cell proliferation, while higher concentrations led to induction of apoptosis Helmis et al 2013).…”

“…The [ 3 H]-InsPs in the supernatants were analyzed by anion exchange chromatography as described by Agarwal et al (2010). Briefly, clear supernatants were subjected to gravity fed columns packed with AG-1×8 anion exchange resin (formate form, 100-200 mesh size, Bio-Rad Laboratories, Hercules, CA).…”

Physicochemical characterization of Theobroma cacao L. mucilage, in Ecuadorian coast

“…This compound has been employed in growth inhibition assays of human tumor cell lines (De Lima et al, 2015), as a protective agent in fishes with copper exposure (Jiang et al, 2014), as indicator during cellular apoptosis (Agarwal et al, 2010). Other compound: Maltose (0.02%) is a disaccharide that it has too many applications.…”

Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1

“…According to the literature, inositol polyphosphates (InsPs) were shown to play signaling roles in the regulation of calcium mobilization, cell growth, vesicular transport, gene expression, and export of mRNA and apoptosis [30][31][32][33][34]. MINPP1 is an ER luminal soluble protein and dephosphorylates InsPs by removing specifically phosphate group at position 3 and association with apoptosis has been described extensively [17,[35][36][37][38][39][40][41]. MINPP1 is the only ER resident enzyme that can hydrolyze inositol pentakisphosphate and inositol hexakisphosphate and it exhibits characteristics of a stress-responsive molecule during ER stress-induced apoptosis regardless of the underlying involved mechanisms [42].…”