Dual Roles of P2 Purinergic Receptors in Insulin-stimulated Leptin Production and Lipolysis in Differentiated Rat White Adipocytes

Lee, Hyun; Jun, Dong-Jae; Suh, Byung‐Chang; Choi, Bo-Hwa; Lee, Jonghee; Do, Myoung‐Sool; Suh, Byung Sun; Ha, Hyunjung; Kim, Kyong‐Tai

doi:10.1074/jbc.m411253200

Cited by 46 publications

(45 citation statements)

References 57 publications

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“…This cannot be considered valid proof of P2Y 11 receptor activation, since ATP might also act through P2Y 2 to stimulate cellular release of arachidonic acid, which can act in an autocrine fashion after conversion to prostaglandins and result in a rise in intracellular cAMP through prostaglandin receptors [85]. This is also evidenced by the observation that stimulation with ATP results in significant cAMP increases in various cell types in rats and mice [11][12][13][14][15][16]86]. This shows that the mechanism for an increase in intracellular cAMP following ATP stimulation is not by itself proof of P2Y 11 receptor activation.…”

Section: Selective P2y 11 Activation and Inhibitionmentioning

confidence: 99%

A critical look at the function of the P2Y11 receptor

Dreisig

Kornum

2016

Purinergic Signalling

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The P2Y 11 receptor is a member of the purinergic receptor family. It has been overlooked, somewhat due to the lack of a P2ry11 gene orthologue in the murine genome, which prevents the generation of knockout mice, which have been so helpful for defining the roles of other P2Y receptors. Furthermore, some of the studies reported to date have methodological shortcomings, making it difficult to determine the function of P2Y 11 with certainty. In this review, we discuss the lack of a murine BP2Y 11 -like receptor^and highlight the limitations of the currently available methods used to investigate the P2Y 11 receptor. These methods include protein recognition with antibodies that show very little specificity, gene expression studies that completely overlook the existence of a fusion transcript between the adjacent PPAN gene and P2RY11, and agonists/antagonists reported to be specific for the P2Y 11 receptor but which have not been tested for activity on numerous other adenosine 5′-triphosphate (ATP)-binding receptors. We suggest a set of criteria for evaluating whether a dataset describes effects mediated by the P2Y 11 receptor. Following these criteria, we conclude that the current evidence suggests a role for P2Y 11 in immune activation with cell typespecific effects.

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Section: Selective P2y 11 Activation and Inhibitionmentioning

confidence: 99%

A critical look at the function of the P2Y11 receptor

Dreisig

Kornum

2016

Purinergic Signalling

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“…After transfection, the cells were processed for western blotting and/or MTT assay as indicated. Effect of PKC␦ siRNA in primary cortical cells was confirmed by quantitative RT-PCR, which was performed as described in detail elsewhere (Lee et al, 2005). Primers used in PCR were as follows: GAPDH forward 5Ј-GCC-ATCAATGACCCCTTCATT-3Ј and reverse 5Ј-GCTCCTGGAAGATGGTGATGG-3Ј; PKC␦ forward 5Ј-TCTGGGAGTGACATCCTAGACAACAACGGG-3Ј and reverse 5Ј-CAGATGATCTCAGCTGCATAAAACGTAGCC-3Ј.…”

Section: Pkc␦ Kinase Assaymentioning

confidence: 99%

Protein kinase Cδ-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death

Choi

Hur

Lee

et al. 2006

Journal of Cell Science

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111

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Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a dual-specificity phosphatase that is involved in the regulation of cell survival, differentiation and apoptosis through inactivating MAPKs by dephosphorylation. Here, we provide evidence for a role of MKP-1 in the glutamate-induced cell death of HT22 hippocampal cells and primary mouse cortical neurons. We suggest that, during glutamate-induced oxidative stress, protein kinase C (PKC) δ becomes activated and induces sustained activation of extracellular signal-regulated kinase 1/2 (ERK1/2) through a mechanism that involves degradation of MKP-1. Glutamate-induced activation of ERK1/2 was blocked by inhibition of PKCδ, confirming that ERK1/2 is regulated by PKCδ. Prolonged exposure to glutamate caused reduction in the protein level of MKP-1, which correlated with the sustained activation of ERK1/2. Furthermore, knockdown of endogenous MKP-1 by small interfering (si)RNA resulted in pronounced enhancement of ERK1/2 phosphorylation accompanied by increased cytotoxicity under glutamate exposure. In glutamate-treated cells, MKP-1 was polyubiquitylated and proteasome inhibitors markedly blocked the degradation of MKP-1. Moreover, inhibition of glutamate-induced PKCδ activation suppressed the downregulation and ubiquitylation of MKP-1. Taken together, these results demonstrate that activation of PKCδ triggers degradation of MKP-1 through the ubiquitin-proteasome pathway, thereby contributing to persistent activation of ERK1/2 under glutamate-induced oxidative toxicity.

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“…Calcium Measurements-Intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) was determined using the fluorescent Ca 2ϩ indicator, fura-2, as previously reported (25). Briefly, SN4741 cells were incubated with 3 M (final concentration) fura-2 pentaacetoxymethyl ester (fura-2/AM) in complete medium at 37°C with stirring for 50 min.…”

Section: Methodsmentioning

confidence: 99%

“…Western Blot-Immunoblot analysis was performed as described previously (25). SN4741 cells were plated on 60-mm tissue culture dishes and transfected with siRNA targeting P2X 7 R as indicated.…”

Section: Methodsmentioning

confidence: 99%

Extracellular ATP Mediates Necrotic Cell Swelling in SN4741 Dopaminergic Neurons through P2X7 Receptors

Jun

Kim

Jung

et al. 2007

Journal of Biological Chemistry

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Extracellular ATP has recently been identified as an important regulator of cell death in response to pathological insults. When SN4741 cells, which are dopaminergic neurons derived from the substantia nigra of transgenic mouse embryos, are exposed to ATP, cell death occurs. This cell death is associated with prominent cell swelling, loss of ER integrity, the formation of many large cytoplasmic vacuoles, and subsequent cytolysis and DNA release. In addition, the cleavage of caspase-3, a hallmark of apoptosis, is induced by ATP treatment. However, caspase inhibitors do not overcome ATP-induced cell death, indicating that both necrosis and apoptosis are associated with ATP-induced cell death and suggesting that a necrotic event might override the apoptotic process. In this study we also found that P2X 7 receptors (P2X 7 Rs) are abundantly expressed in SN4741 cells, and both ATP-induced swelling and cell death are reversed by pretreatment with the P2X 7 Rs antagonist, KN62, or by knock-down of P2X 7 Rs with small interfering RNAs. Therefore, extracellular ATP release from injured tissues may act as an accelerating factor in necrotic SN4741 dopaminergic cell death via P2X 7 Rs. Parkinson disease (PD)2 is an idiopathic neurodegenerative disorder characterized by selective cell death of dopaminergic neurons in the substantia nigra (1). The symptoms of PD only become apparent when more than 50% of the dopaminergic neurons in the substantia nigra pars compacta are lost, which leads to an over 80% reduction in dopamine levels in the striatum (2). Epidemiological studies and pathological analyses demonstrate that sporadic PD with late onset occurs in 95% of patients, whereas the remaining 5% of PD cases are familial diseases with early onset (1, 2). Although the etiological causes of PD have not been fully elucidated, several factors have been suggested as causes of neuronal degeneration. These include environmental toxins, genetic factors, and mitochondrial dysfunction as well as proteasomal impairment and oxidative stress (3). Recently, however, there has been increasing recognition of the possible role of neuro-inflammation as a major factor in the pathogenesis of PD (4). The inflammatory component is an attractive target for therapeutic intervention. It is now generally accepted that high levels of extracellular ATP may be released under pathological conditions such as inflammation, trauma, and stress. The role of extracellular ATP and purinergic receptors in neurodegeneration is one of the focus areas of cell death research (5).P2X 7 receptors (P2X 7 Rs) are unusual purinergic receptors in that they can exist in two functional states: either as cationselective channels or as nonselective pores (6). The permeability transition of P2X 7 Rs from channel to pore occurs either upon sustained stimulation with high ATP concentrations or repeated pulses of ATP application (7). Seven members of the P2X receptor family have been cloned that share the same predicted structure with two transmembrane-spanning domains. These are a...

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Dual Roles of P2 Purinergic Receptors in Insulin-stimulated Leptin Production and Lipolysis in Differentiated Rat White Adipocytes

Cited by 46 publications

References 57 publications

A critical look at the function of the P2Y11 receptor

A critical look at the function of the P2Y11 receptor

Protein kinase Cδ-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death

Extracellular ATP Mediates Necrotic Cell Swelling in SN4741 Dopaminergic Neurons through P2X7 Receptors

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