title: Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for Minpp1 in cellular stress response.
abstract: Inositol polyphosphates represent a group of differentially phosphorylated inositol metabolites, many of which are implicated to regulate diverse cellular processes such as calcium mobilization, vesicular trafficking, differentiation, apoptosis, etc. The metabolic network of these compounds is complex and tightly regulated by various kinases and phosphatases present predominantly in the cytosol. Multiple inositol polyphosphate phosphatase 1 (Minpp1) is the only known endoplasmic reticulum (ER) luminal enzyme that hydrolyzes various inositol polyphosphates in vitro as well as in vivo conditions. However, access of the Minpp1 to cytosolic substrates has not yet been demonstrated clearly and hence its physiological function. In this study, we examined a potential role for Minpp1 in ER stress-induced apoptosis. We generated a custom antibody and characterized its specificity to study the expression of Minpp1 protein in multiple mammalian cells under experimentally induced cellular stress conditions. Our results demonstrate a significant increase in the expression of Minpp1 in response to a variety of cellular stress conditions. The protein expression was corroborated with the expression of its mRNA and enzymatic activity. Further, in an attempt to link the role of Minpp1 to apoptotic stress, we studied the effect of Minpp1 expression on apoptosis following silencing of the Minpp1 gene by its specific siRNA. Our results suggest an attenuation of apoptotic parameters following knockdown of Minpp1. Thus, in addition to its known role in inositol polyphosphate metabolism, we have identified a novel role for Minpp1 as a stress-responsive protein. In summary, our results provide, for the first time, a probable link between ER stress-induced apoptosis and Minpp1 expression.
authors.affiliation: Department of Biology, University of Arkansas at Little Rock, 2801 S University Avenue, Little Rock, AR, 72204, USA.
authors.forename: Surya P
authors.initials: SP
authors.lastname: Kilaparty
authors.affiliation: Department of Biology, University of Arkansas at Little Rock, 2801 S University Avenue, Little Rock, AR, 72204, USA.|Alexion Pharmaceuticals, Inc., Cheshire, CT, 06410, USA.
authors.forename: Rakhee
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Department of Biology, University of Arkansas at Little Rock, 2801 S University Avenue, Little Rock, AR, 72204, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
authors.forename: Krishnaswamy
authors.initials: K
authors.lastname: Kannan
authors.affiliation: Department of Biology, University of Arkansas at Little Rock, 2801 S University Avenue, Little Rock, AR, 72204, USA. nali@ualr.edu.
authors.forename: Nawab
authors.initials: N
authors.lastname: Ali
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D000906:Antibodies; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D010744:Phosphoric Monoester Hydrolases; C064119:multiple inositol-polyphosphate phosphatase
keywords: Apoptosis; ER stress; Endoplasmic reticulum; Inositol phosphates; Minpp1; Multiple inositol polyphosphate phosphatase