Increased susceptibility to ATP via alteration of P2X receptor function in dystrophic mdx mouse muscle cells

Yeung, Davy; Zabłocki, Krzysztof; Lien, Chun-Fu; Jiang, Taiwen; Arkle, S.; Brutkowski, Wojciech; Brown, James F.; Lochmüller, Hanns; Simon, József; Barnard, Eric A.; Górecki, Dariusz C.

doi:10.1096/fj.05-4022com

Cited by 61 publications

(99 citation statements)

References 64 publications

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“…P2X7 receptors are widely distributed in immunocompetent cells of the central and peripheral nervous system, including SC, and the pathogenetic role of P2X7 and the therapeutic potential of P2X7 antagonists are being increasingly recognized in several neurological disorders, including peripheral neuropathies (32,36,51). It is also noteworthy that overexpression of P2X7 and the consequent increase of Ca 2ϩ influx have been implicated in the pathogenesis of Duchenne muscular dystrophy (52).…”

Section: Discussionmentioning

confidence: 99%

P2X7-mediated Increased Intracellular Calcium Causes Functional Derangement in Schwann Cells from Rats with CMT1A Neuropathy

Nobbio

Sturla²,

Fiorese

et al. 2009

Journal of Biological Chemistry

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Charcot-Marie-Tooth disease type 1 (CMT1) 3 is a progressive hereditary motor and sensory neuropathy, characterized by distal muscle wasting and weakness, foot deformities, and severe slowing of nerve conduction, because of progressive demyelination (1). With a prevalence of 1 case in 2500, CMT1 is the most common hereditary neurologic disorder, and in the majority of cases (CMT1A) the disease is associated with a duplication on chromosome 17p11.2 of the gene for PMP22 (peripheral myelin protein 22) (2). PMP22 is a 22-kDa glycoprotein mainly expressed by myelinating Schwann cells (SC) and localized in compact myelin (3). The transgenic rat model of CMT1A, obtained by overexpression of PMP22 (4), confirms a role of PMP22 in the pathogenesis of CMT1A. Both PMP22 overexpression because of gene duplication and point mutations of PMP22 are associated with a CMT1A phenotype.The biochemical mechanisms correlating PMP22 dysfunction with demyelination are still unclear. Some reports indicate that a perturbed homeostasis of the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) might be causally involved in the demyelination process. Conditions inducing an increased [Ca 2ϩ ] i in SC impair cell differentiation and myelination (5, 6), similarly to what occurs in CMT1A. Incubation of intact rat nerves with Ca 2ϩ and ionophores causes a progressive demyelination, spreading from the paranodes and invading regions of formerly compact myelin, which is dependent upon a rise in the [Ca 2ϩ ] i of SC (5). Additional evidence for the detrimental effect of a [Ca 2ϩ ] i elevation on myelin production by SC comes from application of ATP to murine SC monocultures, inducing an immediate and large increase in the [Ca 2ϩ ] i . As a result of ATP treatment, maturation and differentiation of SC, as well as expression of the myelin basic protein and production of compact myelin, are completely prevented (6). Taken together, the above observations indicate that abnormally elevated Ca 2ϩ levels are causally related to impairment of myelin production by SC. * This work was supported in part by Telethon Grants GGP06178 and GUP05007 (to A. S.)

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Section: Discussionmentioning

confidence: 99%

P2X7-mediated Increased Intracellular Calcium Causes Functional Derangement in Schwann Cells from Rats with CMT1A Neuropathy

Nobbio

Sturla²,

Fiorese

et al. 2009

Journal of Biological Chemistry

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“…This is based on our current and previous studies showing that neither the P2X 7 R agonist BzATP (this study) nor its antagonist KN-62 (Scemes et al, 2003) had an impact on progenitor cell migration. Although the P2X 7 receptors have been proposed to be a component of the inflammatory response in astrocytes (Narcisse et al, 2005), and a contributor to pathogenic Ca 2+ entry (Yeung et al, 2006), and cell death (Zhang et al, 2005;Wang et al, 2004), further studies are needed to disclose the impact of these ionotropic receptors on neural progenitor cell (patho) physiology.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1β affects calcium signaling and in vitro cell migration of astrocyte progenitors

Striedinger¹,

Scemes

2008

Journal of Neuroimmunology

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Spontaneous calcium activity of neural progenitors is largely dependent on a paracrine signaling mechanism involving release of ATP and activation of purinergic receptors. Although it is well documented that, in mature astrocytes, cytokines modulate the expression levels of certain purinergic receptors, nothing is known about their impact during early stages of development. Here we provide evidence that conditioned medium from activated microglia as well as interleukin-1β, but not tumor necrosis factor-α, decrease the frequency of calcium oscillations and reduce the rate of "in vitro" migration of astrocyte progenitors. Such alterations were due to changes in activity of two purinergic P2 receptors, and not to the amount of released ATP. These results indicate that Interleukin-1β plays important role during early stages of CNS development, modulating calcium signaling and cell migration.

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“…Evidence for the involvement of purinergic signalling in muscle regeneration may lead to novel therapeutic strategies for the treatment of muscle disease. Immortalized myoblast cell lines derived from the mdx mouse (SC5) and control (dystrophin positive) myoblasts (IMO) from the same parent mouse strain have been used to investigate changes in P2X receptor expression and function in dystrophic muscle [355]. It was shown that a purinergic dystrophic phenotype arises at the earliest myoblast stage of developing dystrophic muscle.…”

Section: Muscular Dystrophymentioning

confidence: 99%

Purinergic signalling in the musculoskeletal system

Burnstock

Arnett

Orriss

2013

Purinergic Signalling

109

114

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It is now widely recognised that extracellular nucleotides, signalling via purinergic receptors, participate in numerous biological processes in most tissues. It has become evident that extracellular nucleotides have significant regulatory effects in the musculoskeletal system. In early development, ATP released from motor nerves along with acetylcholine acts as a cotransmitter in neuromuscular transmission; in mature animals, ATP functions as a neuromodulator. Purinergic receptors expressed by skeletal muscle and satellite cells play important pathophysiological roles in their development or repair. In many cell types, expression of purinergic receptors is often dependent on differentiation. For example, sequential expression of P2X5, P2Y 1 and P2X2 receptors occurs during muscle regeneration in the mdx model of muscular dystrophy. In bone and cartilage cells, the functional effects of purinergic signalling appear to be largely negative. ATP stimulates the formation and activation of osteoclasts, the bone-destroying cells. Another role appears to be as a potent local inhibitor of mineralisation. In osteoblasts, the bone-forming cells, ATP acts via P2 receptors to limit bone mineralisation by inhibiting alkaline phosphatase expression and activity. Extracellular ATP additionally exerts significant effects on mineralisation via its hydrolysis product, pyrophosphate. Evidence now suggests that purinergic signalling is potentially important in several bone and joint disorders including osteoporosis, rheumatoid arthritis and cancers. Strategies for future musculoskeletal therapies might involve modulation of purinergic receptor function or of the ecto-nucleotidases responsible for ATP breakdown or ATP transport inhibitors.

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Increased susceptibility to ATP via alteration of P2X receptor function in dystrophic mdx mouse muscle cells

Cited by 61 publications

References 64 publications

P2X7-mediated Increased Intracellular Calcium Causes Functional Derangement in Schwann Cells from Rats with CMT1A Neuropathy

P2X7-mediated Increased Intracellular Calcium Causes Functional Derangement in Schwann Cells from Rats with CMT1A Neuropathy

Interleukin-1β affects calcium signaling and in vitro cell migration of astrocyte progenitors

Purinergic signalling in the musculoskeletal system

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