Owen W. Nadeau

Novel histone modifications in microglia derived from a mouse model of chronic pain

Ping Zhang, Jennifer Guergues, Amy R. Alleyne, Thomas J. Cirino et autres

As the resident immune cells in the central nervous system, microglia play an important role in the maintenance of its homeostasis. Dysregulation of microglia has been associated with the development and maintenance of chronic pain. However, the relevant molecular pathways remain poorly …

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Global miRNA/proteomic analyses identify miRNAs at 14q32 and 3p21, which contribute to features of chronic iron-exposed fallopian tube epithelial cells

Ravneet Chhabra, Stephanie Rockfield, Jennifer Guergues, Owen W. Nadeau et autres

Malignant transformation of fallopian tube secretory epithelial cells (FTSECs) is a key contributing event to the development of high-grade serous ovarian carcinoma (HGSOC). Our recent findings implicate oncogenic transformative events in chronic iron-exposed FTSECs, including increased expression of oncogenic mediators, increased telomerase …

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Site‐specific identification and validation of hepatic histone nitration in vivo: Implications for alcohol‐induced liver injury

Crystina L. Kriss, Nalvi D. Duro, Owen W. Nadeau, Jennifer Guergues et autres

Oxidative and nitrative stress have been implicated in the molecular mechanisms underlying a variety of biological processes and disease states including cancer, aging, cardiovascular disease, neurological disorders, diabetes, and alcohol-induced liver injury. One marker of nitrative stress is the formation of 3-nitrotyrosine, …

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High Functioning Autism with Missense Mutations in Synaptotagmin-Like Protein 4 (SYTL4) and Transmembrane Protein 187 (TMEM187) Genes: SYTL4- Protein Modeling, Protein-Protein Interaction, Expression Profiling and MicroRNA Studies

Syed K. Rafi, Alberto Fernández‐Jaén, Sara Álvarez, Owen W. Nadeau et autres

We describe a 7-year-old male with high functioning autism spectrum disorder (ASD) and maternally-inherited rare missense variant of Synaptotagmin-like protein 4 (SYTL4) gene (Xq22.1; c.835C>T; p.Arg279Cys) and an unknown missense variant of Transmembrane protein 187 (TMEM187) gene (Xq28; c.708G>T; p. Gln236His). Multiple …

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The regulation of glycogenolysis in the brain

Owen W. Nadeau, Joseph D. Fontes, Gerald M. Carlson

The key regulatory enzymes of glycogenolysis are phosphorylase kinase, a hetero-oligomer with four different types of subunits, and glycogen phosphorylase, a homodimer. Both enzymes are activated by phosphorylation and small ligands, and both enzymes have distinct isoforms that are predominantly expressed in …

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The structure of the large regulatory α subunit of phosphorylase kinase examined by modeling and hydrogen‐deuterium exchange

Mary Ashley Rimmer, Owen W. Nadeau, Jianyi Yang, Antonio Artigues et autres

Abstract Phosphorylase kinase (PhK), a 1.3 MDa regulatory enzyme complex in the glycogenolysis cascade, has four copies each of four subunits, (αβγδ)4, and 325 kDa of unique sequence (the mass of an αβγδ protomer). The α, β and δ subunits are regulatory, …

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Structural characterization of the catalytic γ and regulatory β subunits of phosphorylase kinase in the context of the hexadecameric enzyme complex

Mary Ashley Rimmer, Owen W. Nadeau, Antonio Artigues, Gerald M. Carlson

In the tightly regulated glycogenolysis cascade, the breakdown of glycogen to glucose-1-phosphate, phosphorylase kinase (PhK) plays a key role in regulating the activity of glycogen phosphorylase. PhK is a 1.3 MDa hexadecamer, with four copies each of four different subunits (α, β, …

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Protein Structural Analysis via Mass Spectrometry-Based Proteomics

Antonio Artigues, Owen W. Nadeau, Mary Ashley Rimmer, María T. Villar et autres

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Activation of Phosphorylase Kinase by Physiological Temperature

Julio E. Herrera, Jackie A. Thompson, Mary Ashley Rimmer, Owen W. Nadeau et autres

In the six decades since its discovery, phosphorylase kinase (PhK) from rabbit skeletal muscle has usually been studied at 30 °C; in fact, not a single study has examined functions of PhK at a rabbit's body temperature, which is nearly 10 °C …

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Mass Spectrometric Analysis of Surface-Exposed Regions in the Hexadecameric Phosphorylase Kinase Complex

Mary Ashley Rimmer, Antonio Artigues, Owen W. Nadeau, María T. Villar et autres

Phosphorylase kinase (PhK) is a 1.3 MDa (αβγδ)4 enzyme complex, in which αβγδ protomers associate in D2 symmetry to form two large octameric lobes that are interconnected by four bridges. The approximate locations of the subunits have been mapped in low-resolution cryo-electron …

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A model for activation of the hexadecameric phosphorylase kinase complex deduced from zero‐length oxidative crosslinking

Jackie A. Thompson, Owen W. Nadeau, Gerald M. Carlson

Phosphorylase kinase (PhK) is a hexadecameric (αβγδ)(4) enzyme complex that upon activation by phosphorylation stimulates glycogenolysis. Due to its large size (1.3 MDa), elucidating the structural changes associated with the activation of PhK has been challenging, although phosphoactivation has been linked with …

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Physicochemical changes in phosphorylase kinase induced by its cationic activator Mg2+

Weiya Liu, Owen W. Nadeau, Jessica M. Sage, Gerald M. Carlson

For over four decades free Mg(2+) ions, that is, those in excess of MgATP, have been reported to affect a wide variety of properties of phosphorylase kinase (PhK), including its affinity for other molecules, proteolysis, chemical crosslinking, phosphorylation, binding to certain monoclonal …

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