Publications by authors named "Mary E Skinner"

5 Publications

  • Page 1 of 1

SIRT3 Regulates Macrophage-Mediated Inflammation in Diabetic Wound Repair.

J Invest Dermatol 2019 12 15;139(12):2528-2537.e2. Epub 2019 Jun 15.

Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA. Electronic address:

Control of inflammation is critical for the treatment of nonhealing wounds, but a delicate balance exists between early inflammation that is essential for normal tissue repair and the pathologic inflammation that can occur later in the repair process. This necessitates the development of novel therapies that can target inflammation at the appropriate time during repair. Here, we found that SIRT3 is essential for normal healing and regulates inflammation in wound macrophages after injury. Under prediabetic conditions, SIRT3 was decreased in wound macrophages and resulted in dysregulated inflammation. In addition, we found that FABP4 regulates SIRT3 in human blood monocytes, and inhibition of FABP4 in wound macrophages decreases inflammatory cytokine expression, making FABP4 a viable target for the regulation of excess inflammation and wound repair in diabetes. Using a series of ex vivo and in vivo studies with genetically engineered mouse models and diabetic human monocytes, we showed that FABP4 expression is epigenetically upregulated in diabetic wound macrophages and, in turn, diminishes SIRT3 expression, thereby promoting inflammation. These findings have significant implications for controlling inflammation and promoting tissue repair in diabetic wounds.
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http://dx.doi.org/10.1016/j.jid.2019.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185380PMC
December 2019

Sirtuins: guardians of mammalian healthspan.

Trends Genet 2014 Jul 28;30(7):271-86. Epub 2014 May 28.

Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Institute of Gerontology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

The first link between sirtuins and longevity was made 15 years ago in yeast. These initial studies sparked efforts by many laboratories working in diverse model organisms to elucidate the relations between sirtuins, lifespan, and age-associated dysfunction. Here, we discuss the current understanding of how sirtuins relate to aging. We focus primarily on mammalian sirtuins SIRT1, SIRT3, and SIRT6, the three sirtuins for which the most relevant data are available. Strikingly, a large body of evidence now indicates that these and other mammalian sirtuins suppress a variety of age-related pathologies and promote healthspan. Moreover, increased expression of SIRT1 or SIRT6 extends mouse lifespan. Overall, these data point to important roles for sirtuins in promoting mammalian health, and perhaps in modulating the aging process.
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http://dx.doi.org/10.1016/j.tig.2014.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077918PMC
July 2014

Mass spectrometry-based detection of protein acetylation.

Methods Mol Biol 2013 ;1077:81-104

Cell Signaling Technology, Danvers, MA, USA.

Improved sample preparation techniques and increasingly sensitive mass spectrometry (MS) analysis have revolutionized the study of protein post-translational modifications (PTMs) (Rush et al., Nat Biotechnol 23:94-101, 2005). Here, we describe a general approach for immunopurification and MS-based identification of acetylated proteins in biological samples. This approach is useful to characterize changes in the acetylome in response to biological interventions (Schwer et al., Aging Cell 8:604-606, 2009).
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http://dx.doi.org/10.1007/978-1-62703-637-5_6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954751PMC
April 2014

SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways.

Mol Cell 2013 Jun;50(6):919-30

Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.

Protein function is regulated by diverse posttranslational modifications. The mitochondrial sirtuin SIRT5 removes malonyl and succinyl moieties from target lysines. The spectrum of protein substrates subject to these modifications is unknown. We report systematic profiling of the mammalian succinylome, identifying 2,565 succinylation sites on 779 proteins. Most of these do not overlap with acetylation sites, suggesting differential regulation of succinylation and acetylation. Our analysis reveals potential impacts of lysine succinylation on enzymes involved in mitochondrial metabolism; e.g., amino acid degradation, the tricarboxylic acid cycle (TCA) cycle, and fatty acid metabolism. Lysine succinylation is also present on cytosolic and nuclear proteins; indeed, we show that a substantial fraction of SIRT5 is extramitochondrial. SIRT5 represses biochemical activity of, and cellular respiration through, two protein complexes identified in our analysis, pyruvate dehydrogenase complex and succinate dehydrogenase. Our data reveal widespread roles for lysine succinylation in regulating metabolism and potentially other cellular functions.
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http://dx.doi.org/10.1016/j.molcel.2013.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769971PMC
June 2013

Deep sequencing of voodoo lily (Amorphophallus konjac): an approach to identify relevant genes involved in the synthesis of the hemicellulose glucomannan.

Planta 2011 Sep 3;234(3):515-26. Epub 2011 May 3.

Energy Biosciences Institute, University of California-Berkeley, 130 Calvin Laboratory MC 5230, Berkeley, CA, USA.

A Roche 454 cDNA deep sequencing experiment was performed on a developing corm of Amorphophallus konjac--also known as voodoo lily. The dominant storage polymer in the corm of this plant is the polysaccharide glucomannan, a hemicellulose known to exist in the cell walls of higher plants and a major component of plant biomass derived from softwoods. A total of 246 mega base pairs of sequence data was obtained from which 4,513 distinct contigs were assembled. Within this voodoo lily expressed sequence tag collection genes representing the carbohydrate related pathway of glucomannan biosynthesis were identified, including sucrose metabolism, nucleotide sugar conversion pathways for the formation of activated precursors as well as a putative glucomannan synthase. In vivo expression of the putative glucomannan synthase and subsequent in vitro activity assays unambiguously demonstrate that the enzyme has indeed glucomannan mannosyl- and glucosyl transferase activities. Based on the expressed sequence tag analysis hitherto unknown pathways for the synthesis of GDP-glucose, a necessary precursor for glucomannan biosynthesis, could be proposed. Moreover, the results highlight transcriptional bottlenecks for the synthesis of this hemicellulose.
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http://dx.doi.org/10.1007/s00425-011-1422-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162142PMC
September 2011