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001-es BibID:BIBFORM105186
035-os BibID:(cikkazonosító)1037230 (Scopus)85142638283 (WOS)000890212100001 (PubMed)36439266
Első szerző:Szabó László (molekuláris biológus)
Cím:The mechanosensitive Piezo1 channels contribute to the arterial medial calcification / Szabó, László; Balogh, Norbert; Tóth, Andrea; Angyal, Ágnes; Gönczi, Mónika; Csiki, Dávid Máté; Tóth, Csaba; Balatoni, Ildikó; Jeney, Viktória; Csernoch, László; Dienes, Beatrix
Dátum:2022
ISSN:1664-042X
Megjegyzések:Vascular calcification (VC) is associated with a number of cardiovascular diseases, as well as chronic kidney disease. The role of smooth muscle cells (SMC) has already been widely explored in VC, as has the role of intracellular Ca2+ in regulating SMC function. Increased intracellular calcium concentration ([Ca2+]i) in vascular SMC has been proposed to stimulate VC. However, the contribution of the non-selective Piezo1 mechanosensitive cation channels to the elevation of [Ca2+]i, and consequently to the process of VC has never been examined. In this work the essential contribution of Piezo1 channels to arterial medial calcification is demonstrated. The presence of Piezo1 was proved on human aortic smooth muscle samples using immunohistochemistry. Quantitative PCR and Western blot analysis confirmed the expression of the channel on the human aortic smooth muscle cell line (HAoSMC). Functional measurements were done on HAoSMC under control and calcifying condition. Calcification was induced by supplementing the growth medium with inorganic phosphate (1.5 mmol/L, pH 7.4) and calcium (CaCl2, 0.6 mmol/L) for 7 days. Measurement of [Ca2+]i using fluorescent Fura-2 dye upon stimulation of Piezo1 channels (either by hypoosmolarity, or Yoda1) demonstrated significantly higher calcium transients in calcified as compared to control HAoSMCs. The expression of mechanosensitive Piezo1 channel is augmented in calcified arterial SMCs leading to a higher calcium influx upon stimulation. Activation of the channel by Yoda1 (10 ?mol/L) enhanced calcification of HAoSMCs, while Dooku1, which antagonizes the effect of Yoda1, reduced this amplification. Application of Dooku1 alone inhibited the calcification. Knockdown of Piezo1 by siRNA suppressed the calcification evoked by Yoda1 under calcifying conditions. Our results demonstrate the pivotal role of Piezo1 channels in arterial medial calcification.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
vascular smooth muscle
mechanosensation
Piezo1
calcification
intracellular calcium concentration
Yoda1
Dooku1
Megjelenés:Frontiers in Physiology. - 13 (2022), p. 1037230. -
További szerzők:Balogh Norbert (1988-) (molekuláris biológus) Tóth Andrea (1992-) (molekuláris biológus) Angyal Ágnes (1987-) (molekuláris biológus) Gönczi Mónika (1974-) (élettanász) Csiki Dávid Máté (1993-) (biomérnök) Tóth Csaba (1968-) (sebész, érsebész) Balatoni Ildikó (1970-) (orvos) Jeney Viktória (1971-) (vegyész, kémia tanár) Csernoch László (1961-) (élettanász) Dienes Beatrix (1972-) (élettanász, molekuláris biológus)
Pályázati támogatás:EFOP-3.6.2-16-2017-00006
EFOP
TKP2020-NKA-04
Egyéb
TKP2021-EGA-18
Egyéb
GINOP-2.3.3-15-2016-00020
GINOP
K131535
OTKA
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DOI
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2.

001-es BibID:BIBFORM090185
035-os BibID:(cikkazonosító)601090 (WoS)000604306200001 (Scopus)85098756322
Első szerző:Sztretye Mónika (élettanász, elektrofiziológus)
Cím:The Role of Orai1 in Regulating Sarcoplasmic Calcium Release, Mitochondrial Morphology and Function in Myostatin Deficient Skeletal Muscle / Mónika Sztretye, Zoltán Singlár, Norbert Balogh, Gréta Kis, Péter Szentesi, Ágnes Angyal, Ildikó Balatoni, László Csernoch, Beatrix Dienes
Dátum:2020
ISSN:1664-042X
Megjegyzések:In mice a naturally occurring 12-bp deletion in the myostatin gene is considered responsible for the compact phenotype (MstnCmpt?dl1Abc, Cmpt) labeled by a tremendous increase in body weight along with signs of muscle weakness, easier fatigability, decreased Orai1 expression and store operated calcium entry (SOCE). Here, on the one hand, Cmpt fibers were reconstructed with venus-Orai1 but this failed to restore SOCE. On the other hand, the endogenous Orai1 was silenced in fibers from wild type C57Bl6 mice which resulted in ?70% of Orai1 being silenced in whole muscle homogenates as confirmed by Western blot, accompanied by an inhibitory effect on the voltage dependence of SR calcium release that manifested in a slight shift toward more positive potential values. This maneuver completely hampered SOCE. Our observations are consistent with the idea that Orai1 channels are present in distinct pools responsible for either a rapid refilling of the SR terminal cisternae connected to each voltage-activated calcium transient, or a slow SOCE associated with an overall depletion of calcium in the SR lumen. Furthermore, when Cmpt cells were loaded with the mitochondrial membrane potential sensitive dye TMRE, fiber segments with depolarized mitochondria were identified covering on average 26.5 ? 1.5% of the fiber area. These defective areas were located around the neuromuscular junction and displayed significantly smaller calcium transients. The ultrastructural analysis of the Cmpt fibers revealed changes in the mitochondrial morphology. In addition, the mitochondrial calcium uptake during repetitive stimulation was higher in the Cmpt fibers. Our results favor the idea that reduced function and/or expression of SOCE partners (in this study Orai1) and mitochondrial defects could play an important role in muscle weakness and degeneration associated with certain pathologies, perhaps including loss of function of the neuromuscular junction and aging.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
SOCE
myostatin deficiency
excitation contraction coupling
mithochondrial defect
mitochondrial calcium uptake
Megjelenés:Frontiers in Physiology. - 11 (2020), p. 1-15. -
További szerzők:Singlár Zoltán (1994-) (biotechnológus) Balogh Norbert (1988-) (molekuláris biológus) Kis Gréta (1979-) (molekuláris biológus) Szentesi Péter (1967-) (élettanász) Angyal Ágnes (1987-) (molekuláris biológus) Balatoni Ildikó (1970-) (orvos) Csernoch László (1961-) (élettanász) Dienes Beatrix (1972-) (élettanász, molekuláris biológus)
Pályázati támogatás:PD-108476
Egyéb
PD-128370
Egyéb
GINOP-2.3.2-15-2016-00044
GINOP
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