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Cell Stress and Chaperones

, Volume 21, Issue 4, pp 593–608 | Cite as

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

  • Surya P. Kilaparty
  • Rakhee Agarwal
  • Pooja Singh
  • Krishnaswamy Kannan
  • Nawab AliEmail author
Original Paper

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.

Keywords

Inositol phosphates Apoptosis Multiple inositol polyphosphate phosphatase Minpp1 ER stress Endoplasmic reticulum 

Notes

Acknowledgments

This work was supported in part by funds from NASA-EPSCoR, NSF-EPSCoR/P3 Asset II, Arkansas Space Grant Consortium, and Kathleen Thomsen-Hall Charitable Foundation. We also acknowledge partial support from the Center for Advanced Surface Engineering, under the National Science Foundation Grant No. IIA-1457888 and the Arkansas EPSCoR Program, ASSET III. Dr. Kilaparty thanks UALR Tech Launch for a graduate assistantship. The authors thank Dr. Waqar Majeed, UALR Nanotechnology Center, for assistance with siRNA technique and Ms. Andrea Harris and Ms. Aarthi Kannan of the University of Arkansas for Medical Sciences for assistance with flow cytometry and preparation of the manuscript, respectively.

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12192_2016_684_Fig10_ESM.gif (218 kb)
Supplementary Fig. 1

Analysis of Minpp1 expression in different mammalian cell lines during apoptosis. MC3T3-E1, PanC1, and SW480 cells were treated with cisplatin (25–200 mM) for 24 h. One set of cells was processed for SDS-PAGE and western blotting for Minpp1 expression as detailed in the “Materials and methods.” The western blots shown are representative experiments repeated independently at least three times on all three cell lines with various treatments. Another set of cells was processed for the assessment of apoptosis following acridine orange/ethidium bromide staining. A minimum of 200 cells were counted from five random fields and percentage of cells undergoing apoptosis was determined as detailed in “Materials and methods” section. The bars indicate the means ± S.E. from three different experiments performed in triplicates. (GIF 217 kb)

12192_2016_684_MOESM1_ESM.tif (164 kb)
High resolution (TIF 164 kb)

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Copyright information

© Cell Stress Society International 2016

Authors and Affiliations

  • Surya P. Kilaparty
    • 1
  • Rakhee Agarwal
    • 1
    • 2
  • Pooja Singh
    • 1
  • Krishnaswamy Kannan
    • 3
  • Nawab Ali
    • 1
    Email author
  1. 1.Department of BiologyUniversity of Arkansas at Little RockLittle RockUSA
  2. 2.Alexion Pharmaceuticals, Inc.CheshireUSA
  3. 3.Department of Internal MedicineUniversity of Arkansas for Medical SciencesLittle RockUSA

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