Zhan‐Guo Gao

Senescence caused by telomerase inactivation in myeloid, mesenchymal, and endothelial cells has distinct effects on cancer progression

Joseph E. Rupert, Zhan‐Guo Gao, Yongmei Yu, Mikhail G. Kolonin

The effects of cell senescence in individual cell populations of the tumor microenvironment (TME) on cancer progression remain unclear. Here, we investigated the effects of cell senescence caused by inactivation of the catalytic subunit of telomerase (Tert) in distinct TME components. We …

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Caloric Restriction and Telomere Preservation in TERT Knockout Adipocyte Progenitors Does Not Rescue Mice From Metabolic Dysfunction due to a TERT Function in Adipocyte Mitochondria

Zhan‐Guo Gao, Yongmei Yu, Kristin L Eckel‐Mahan, Mikhail G. Kolonin

Inactivation of telomerase (TERT) in adipocyte progenitor cells (APC) expedites telomere attrition, and the onset of diabetes in mice fed high-fat diet (HFD), which promotes APC over-proliferation and replicative senescence. Here, we show that time-restricted feeding or caloric restriction in the postnatal …

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Lipid Trolling to Optimize A3 Adenosine Receptor-Positive Allosteric Modulators (PAMs)

Balaram Pradhan, Matteo Pavan, Courtney L. Fisher, Veronica Salmaso et autres

A 3 adenosine receptor (A 3 AR) positive allosteric modulators (PAMs) (2,4-disubstituted-1 H -imidazo[4,5- c ]quinolin-4-amines) allosterically increase the E max of A 3 AR agonists, but not potency, due to concurrent orthosteric antagonism. Following mutagenesis/homology modeling of the proposed lipid-exposed allosteric …

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Structural Modification and Biological Evaluation of 2,8-Disubstituted Adenine and Its Nucleosides as A2A Adenosine Receptor Antagonists: Exploring the Roles of Ribose at Adenosine Receptors

Gibae Kim, Dnyandev B. Jarhad, Grim Lee, Gyudong Kim et autres

Building on the preceding structural analysis and a structure–activity relationship (SAR) of 8-aryl-2-hexynyl nucleoside hA 2A AR antagonist 2a, we strategically inverted C2/C8 substituents and eliminated the ribose moiety. These modifications aimed to mitigate potential steric interactions between ribose and adenosine receptors. …

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A2B adenosine receptor-mediated intracellular calcium mobilization: Involvement of Gi, Gq, Gs, β-arrestins, and protein kinase C

Zhan‐Guo Gao, Kenneth A. Jacobson

Terpenes from Cannabis sativa induce antinociception in a mouse model of chronic neuropathic pain via activation of adenosine A2A receptors

Abigail M. Schwarz, Attila I. Keresztes, Thai Bui, Ryan Hecksel et autres

ABSTRACT: Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa . A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies …

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Mesenchymal-specific Alms1 knockout in mice recapitulates metabolic features of Alström syndrome

Eleanor J. McKay, Ineke H. N. Luijten, Xiong Weng, Pablo B. Martínez de Morentin et autres

OBJECTIVE: Alström Syndrome (AS), caused by biallelic ALMS1 mutations, includes obesity with disproportionately severe insulin resistant diabetes, dyslipidemia, and fatty liver. Prior studies suggest that hyperphagia is accounted for by loss of ALMS1 function in hypothalamic neurones, whereas disproportionate metabolic complications may …

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Machine learning-aided search for ligands of P2Y6 and other P2Y receptors

Ana C. Puhl, Sarah A. Lewicki, Zhan‐Guo Gao, Asmita Pramanik et autres

Abstract The P2Y6 receptor, activated by uridine diphosphate (UDP), is a target for antagonists in inflammatory, neurodegenerative, and metabolic disorders, yet few potent and selective antagonists are known to date. This prompted us to use machine learning as a novel approach to …

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Abstract 2957: Senescence of stromal, endothelial, and myeloid cells in the tumor microenvironment has distinct effects on cancer progression

Joseph E. Rupert, Zhan‐Guo Gao, Yongmei Yu, Mikhail G. Kolonin

Abstract Accumulation of senescent cells, undermining the function of vital organs, is a culprit of aging. The effects of senescence in different types of cells on tumor growth and metastasis remain incompletely characterized. Cell senescence has been shown to result from inactivation …

Endothelial‐specific telomerase inactivation causes telomere‐independent cell senescence and multi‐organ dysfunction characteristic of aging

Zhan‐Guo Gao, Rafael González Bravo, Joseph E. Rupert, Rachel Van Drunen et autres

It has remained unclear how aging of endothelial cells (EC) contributes to pathophysiology of individual organs. Cell senescence results in part from inactivation of telomerase (TERT). Here, we analyzed mice with Tert knockout specifically in EC. Tert loss in EC induced transcriptional …

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Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A3 adenosine receptor in HL-60 cells

Zhan‐Guo Gao, Weiping Chen, Ray R. Gao, Jonathan C. Li et autres

Abstract The A3 adenosine receptor (AR) is an important inflammatory and immunological target. However, the underlying mechanisms are not fully understood. Here, we report the gene regulation in HL-60 cells treated acutely with highly selective A3AR agonist MRS5698, positive allosteric modulator (PAM) …

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Membrane mimetic-dependence of GPCR energy landscapes

Naveen Thakur, Arka Prabha Ray, Beining Jin, Nessa Pesaran Afsharian et autres

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