Coupling of P2Y receptors to Ca2+ mobilization in mesenchymal stromal cells from the human adipose tissue

Kotova, Polina D.; Bystrova, M. F.; Rogachevskaja, Olga A.; Хохлов, А. А.; Sysoeva, Veronika; Ткачук, В. А.; Kolesnikov, Stanislav S.

doi:10.1016/j.ceca.2017.11.001

Cited by 23 publications

(22 citation statements)

References 65 publications

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“…Thus, recent findings obtained using single-cell RNAseq technologies identified about 10 distinct MSC subpopulations with different differentiation and secretion abilities [ 3 , 4 ]. MSCs are regulated by a number of endocrine and paracrine signals, many of which activate G-protein coupled receptors (GPCRs), such as acetylcholine [ 5 ], adenosine [ 6 ], angiotensin II [ 7 ], angiotensin 1-7 [ 7 ], ATP [ 8 ], dopamine, GABA [ 9 ], glutamate [ 10 ], histamine [ 11 ], noradrenaline [ 12 ], serotonin [ 13 ], and sphingosine-1-phosphate [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Functional Heterogeneity of Protein Kinase A Activation in Multipotent Stromal Cells

Tyurin‐Kuzmin

Karagyaur

Kulebyakin

et al. 2020

IJMS

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Multipotent stromal cells (MSC) demonstrate remarkable functional heterogeneity; however, its molecular mechanisms remain largely obscure. In this study, we explored MSC response to hormones, which activate Gs-protein / cyclic AMP (cAMP) / protein kinase A (PKA) dependent signaling, at the single cell level using genetically encoded biosensor PKA-Spark. For the first time, we demonstrated that about half of cultured MSCs are not able to activate the cAMP/PKA pathway, possibly due to the limited availability of adenylyl cyclases. Using this approach, we showed that MSC subpopulations responding to various hormones largely overlapped, and the share of responding cells did not exceed 40%. Using clonal analysis, we showed that signaling heterogeneity of MSC could be formed de novo within 2 weeks.

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Section: Introductionmentioning

confidence: 99%

Functional Heterogeneity of Protein Kinase A Activation in Multipotent Stromal Cells

Tyurin‐Kuzmin

Karagyaur

Kulebyakin

et al. 2020

IJMS

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“…MSCs were isolated from the subcutaneous fat tissue by enzymatic digestion as described previously [10]. Briefly, the adipose tissue was extensively washed with 2 volumes of Hank's Balanced Salt Solution (HBSS) containing 5% antibiotic/ antimycotic solution (10,000 units of penicillin, 10,000 μg of streptomycin, and 25 μg of amphotericin B per mL) (HyClone), fragmented, and then digested at 37°C for 1 h in the presence of collagenase (200 U/ml, Sigma-Aldrich) and dispase (10 U/ml, BD Biosciences).…”

Section: Cell Isolation and Culturementioning

confidence: 99%

“…Earlier, we found MSCs from the human adipose tissue to respond to a variety of GPCR ligands, including adrenergic and purinergic agonists, which mobilized cytosolic Ca 2+ by stimulating phospholipase C (PLC) and IP 3 -dependent Ca 2+ release [9,10]. By hydrolyzing PIP 2 , PLC affects the activity of PIP 2 -regulated channels [11], stimulates IP 3 signaling, and produces the essential lipid messenger diacylglycerol (DAG) [12].…”

Section: Introductionmentioning

confidence: 99%

Arachidonic acid hyperpolarizes mesenchymal stromal cells from the human adipose tissue by stimulating TREK1 K⁺ channels

et al. 2019

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The current knowledge of electrogenesis in mesenchymal stromal cells (MSCs) remains scarce. Earlier, we demonstrated that in MSCs from the human adipose tissue, transduction of certain agonists involved the phosphoinositide cascade. Its pivotal effector PLC generates DAG that can regulate ion channels directly or via its derivatives, including arachidonic acid (AA). Here we showed that AA strongly hyperpolarized MSCs by stimulating instantly activating, outwardly rectifying TEA-insensitive K+ channels. Among AA-regulated K+ channels, K2P channels from the TREK subfamily appeared to be an appropriate target. The expression of K2P channels in MSCs was verified by RT-PCR, which revealed TWIK-1, TREK-1, and TASK-5 transcripts. The TREK-1 inhibitor spadin antagonized the electrogenic action of AA, which was simulated by the channel activator BL 1249. This functional evidence suggested that TREK-1 channels mediated AA-dependent hyperpolarization of MSCs. Being mostly silent at rest, TREK-1 negligibly contributed to the “background” K+ current. The dramatic stimulation of TREK-1 channels by AA indicates their involvement in AA-dependent signaling in MSCs.

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“…In mammalians, the P2Y subgroup includes eight GPCRs (P2Y 1,2,4,6,11-14 ) that exhibit certain specificities to nucleotides, depending on species [18,46]. The expression of purinoreceptors in MSCs was analyzed previously, and transcripts for multiple P2Y receptors were detected, namely, P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2Y 13 , and P2Y 14 , while P2Y 12 transcripts were not detected in total MSC preparations [47]. Although this P2Y array is sufficient to account for MSC capability to detect ATP, ADP, and UTP, it was impossible to evaluate a contribution of a particular P2Y isoform based on MSC responses to these natural P2Y agonists ( Figure 2B, E, F).…”

Section: Effects Of Isoform-specific Agonists and Antagonists Of P2y mentioning

confidence: 99%

“…Perhaps, this synthetic ligand is a biased agonist that enables coupling of P2Y 11 to the phosphoinositide cascade by involving only a certain G-protein type, which is absent or relatively less abundant in most of the MSCs. UTP is a full agonist for P2Y 2 and P2Y 4 that were identified in MSCs at the population level [47]. It therefore was unclear whether a particular cell employs either or both of these P2Y receptors for monitoring extracellular UTP.…”

Section: Effects Of Isoform-specific Agonists and Antagonists Of P2y mentioning

confidence: 99%

Calcium Signaling Initiated by Agonists in Mesenchymal Stromal Cells from the Human Adipose Tissue

Kotova¹,

Rogachevskaja²,

Bystrova³

et al. 2018

Calcium and Signal Transduction

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Mesenchymal stromal cells (MSCs) from different sources represent a heterogeneous population of proliferating non-differentiated cells that contain multipotent stem cells capable of originating a variety of mesenchymal cell lineages. By using Ca 2+ imaging and the Ca 2+ dye Fluo-4 , we studied MSCs from the human adipose tissue and examined Ca 2+ signaling initiated by a variety of GPCR ligands, focusing primarily on adrenergic and purinergic agonists. Being characterized by a relative change of Fluo-4 fluorescence, agonist-induced Ca 2+ responses were generated in an "all-or-nothing" fashion. Specifically, at relatively low doses, agonists elicited undetectable responses but initiated quite similar Ca 2+ transients at all concentrations above the threshold. The inhibitory analysis and Ca 2+ /IP 3 uncaging pointed at the phosphoinositide cascade as a pivotal pathway responsible for agonist transduction and implicated Ca 2+-induced Ca 2+ release (CICR) in shaping agonists-dependent Ca 2+ signals. Altogether, our data suggest that agonist transduction in MSCs includes two fundamentally different stages: an agonist initially triggers a local, gradual, and relatively small Ca 2+ signal, which next stimulates CICR to accomplish transduction with a large and global Ca 2+ transient. By involving the trigger-like mechanism CICR, a cell is capable of generating Ca 2+ responses of virtually universal shape and magnitude at different agonist concentrations above the threshold.

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Coupling of P2Y receptors to Ca2+ mobilization in mesenchymal stromal cells from the human adipose tissue

Cited by 23 publications

References 65 publications

Functional Heterogeneity of Protein Kinase A Activation in Multipotent Stromal Cells

Functional Heterogeneity of Protein Kinase A Activation in Multipotent Stromal Cells

Arachidonic acid hyperpolarizes mesenchymal stromal cells from the human adipose tissue by stimulating TREK1 K⁺ channels

Calcium Signaling Initiated by Agonists in Mesenchymal Stromal Cells from the Human Adipose Tissue

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Coupling of P2Y receptors to Ca2+ mobilization in mesenchymal stromal cells from the human adipose tissue

Cited by 23 publications

References 65 publications

Functional Heterogeneity of Protein Kinase A Activation in Multipotent Stromal Cells

Functional Heterogeneity of Protein Kinase A Activation in Multipotent Stromal Cells

Arachidonic acid hyperpolarizes mesenchymal stromal cells from the human adipose tissue by stimulating TREK1 K+ channels

Calcium Signaling Initiated by Agonists in Mesenchymal Stromal Cells from the Human Adipose Tissue

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Arachidonic acid hyperpolarizes mesenchymal stromal cells from the human adipose tissue by stimulating TREK1 K⁺ channels