Adenosine A2B receptors inhibit K+ currents and cell differentiation in cultured oligodendrocyte precursor cells and modulate sphingosine-1-phosphate signaling pathway

In recent years, photobiomodulation (PBM) has been recognized as a physical therapy in wound management. Despite several published research papers, the mechanism underlying photobiomodulation is still not completely understood. The investigation about application of blue light to improve wound healing is a relatively new research area. Tests in selected patients evidenced a stimulation of the healing process in superficial and chronic wounds treated with a blue LED light emitting at 420 nm; a study in animal model pointed out a faster healing process in superficial wound, with an important role of fibroblasts and myofibroblasts. Here, we present a study aiming at evidencing the effects of blue light on the proliferation and metabolism in fibroblasts from healthy skin and keratinocytes. Different light doses (3.43, 6.87, 13.7, 20.6, 30.9 and 41.2 J/cm2) were used to treat the cells, evidencing inhibitory and stimulatory effects following a biphasic dose behavior. Electrophysiology was used to investigate the effects on membrane currents: healthy fibroblasts and keratinocytes showed no significant differences between treated and not treated cells. Raman spectroscopy revealed the mitochondrial Cytochrome C (Cyt C) oxidase dependence on blue light irradiation: a significant decrease in peak intensity of healthy fibroblast was evidenced, while it is less pronounced in keratinocytes. In conclusion, we observed that the blue LED light can be used to modulate metabolism and proliferation of human fibroblasts, and the effects in wound healing are particularly evident when studying the fibroblasts and keratinocytes co-cultures.

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“…Whole-cell patch-clamp recordings were performed in −60 mV clamped-cells as described [18,29]. The following solutions were used.…”

Section: Electrophysiological Recordingsmentioning

confidence: 99%

Photobiomodulation of Human Fibroblasts and Keratinocytes with Blue Light: Implications in Wound Healing

et al. 2021

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“…It is thus tempting to speculate that FTY720-mediated changes in the amplitude and gating of I K(DR) are strongly linked to its binding to S1P receptors inherently in Jurkat cells. In Coppi and colleagues’ work, through inhibiting potassium currents and positively modulating S1P synthesis, A 2B receptor (A 2B R) suppressed cell differentiation in cultured oligodendrocytes progenitor cells [ 37 ]. S1P inhibits delayed rectifier potassium current of guinea pigs’ ventricular myocytes.…”

Section: Discussionmentioning

confidence: 99%

Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes

Chang

Liu

2020

Molecules

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FTY720 (fingolimod), a modulator of sphingosine-1-phosphate receptors, is known to produce the immunomodulatory actions and to be beneficial for treating the relapsing multiple sclerosis. However, whether it exerts any effects on membrane ion currents in immune cells remains largely unknown. Herein, the effects of FTY720 on ionic currents in Jurkat T-lymphocytes were investigated. Cell exposure to FTY720 suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 1.51 μM. Increasing the FTY720 concentration not only decreased the IK(DR) amplitude but also accelerated the inactivation time course of the current. By using the minimal reaction scheme, the effect of FTY720 on IK(DR) inactivation was estimated with a dissociation constant of 3.14 μM. FTY720 also shifted the inactivation curve of IK(DR) to a hyperpolarized potential with no change in the slope factor, and recovery from IK(DR) became slow during the exposure to this compound. Cumulative inactivation for IK(DR) in response to repetitive depolarizations was enhanced in the presence of FTY720. In SEW2871-treated cells, FTY720-induced inhibition of IK(DR) was attenuated. This compound also exerted a stimulatory action on the activity of intermediate-conductance Ca2+-activated K+ channels in Jurkat T-lymphocytes. However, in NSC-34 neuronal cells, FTY720 did not modify the inactivation kinetics of KV3.1-encoded IK(DR), although it suppressed IK(DR) amplitude in these cells. Collectively, the perturbations by FTY720 on different types of K+ channels may contribute to the functional activities of immune cells, if similar findings appear in vivo.

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“…Concerning oligodendrogliogenesis, it is now generally recognized that adenosine plays a key role in OPC maturation. All subtypes of adenosine P1 receptors are expressed during the entire process of OPC maturation (Stevens et al, 2002;Coppi et al, 2013a;Coppi et al, 2020a). Indeed, adenosine is known to be released upon electrical stimulation of nearby neurons to acts as a neuron-glial transmitter that inhibits OPC proliferation and facilitates their differentiation (Stevens et al, 2002).…”

Section: Role Of a 2a Rs And A 2b Rs In Oligodendrogliogenesismentioning

confidence: 99%

“…Successive studies by our laboratory demonstrated that adenosine A 2B R agonists, either the prototypical compound BAY60-6583 or the recently synthetized BAY60-6583-analogue P456 (Betti et al, 2018), not only inhibit sustained I K but also transient I A conductances in cultured OPCs (Coppi et al, 2020a). The effect on I K was mimicked and occluded by forskolin, demonstrating its dependency upon intracellular cAMP increase, consistently with Gs-coupling of A 2A R and A 2B R and with the fact that the Gi-coupled GPR17 (Pugliese et al, 2009b) elicits the opposite effect in OPCs (Coppi et al, 2013b).…”

Section: Role Of a 2a Rs And A 2b Rs In Oligodendrogliogenesismentioning

confidence: 99%

New Insight into the Role of Adenosine in Demyelination, Stroke and Neuropathic Pain

et al. 2021

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Adenosine A2B receptors inhibit K+ currents and cell differentiation in cultured oligodendrocyte precursor cells and modulate sphingosine-1-phosphate signaling pathway

Cited by 25 publications

References 66 publications

Photobiomodulation of Human Fibroblasts and Keratinocytes with Blue Light: Implications in Wound Healing

Photobiomodulation of Human Fibroblasts and Keratinocytes with Blue Light: Implications in Wound Healing

Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes

New Insight into the Role of Adenosine in Demyelination, Stroke and Neuropathic Pain

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