Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for Minpp1 in cellular stress response
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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.
KeywordsInositol phosphates Apoptosis Multiple inositol polyphosphate phosphatase Minpp1 ER stress Endoplasmic reticulum
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.
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Conflict of Interest
The authors declare that they have no conflict of interest.
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