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Characterization of PDGF-Induced Subcellular Calcium Regulation through Calcium Channels in Airway Smooth Muscle Cells by FRET Biosensors.
Ouyang, Mingxing; Zhou, Binqian; Li, Chunmei; Deng, Linhong.
Afiliação
  • Ouyang M; Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, Changzhou 213164, China.
  • Zhou B; Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, Changzhou 213164, China.
  • Li C; School of Pharmacy, Changzhou University, Changzhou 213164, China.
  • Deng L; Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, Changzhou 213164, China.
Biosensors (Basel) ; 14(4)2024 Apr 07.
Article em En | MEDLINE | ID: mdl-38667172
ABSTRACT
The homeostasis of cellular calcium is fundamental for many physiological processes, while the calcium levels remain inhomogeneous within cells. During the onset of asthma, epithelial and inflammatory cells secrete platelet-derived growth factor (PDGF), inducing the proliferation and migration of airway smooth muscle (ASM) to the epidermal layer, narrowing the airway. The regulation of ASM cells by PDGF is closely related to the conduction of calcium signals. In this work, we generated subcellular-targeted FRET biosensors to investigate calcium regulation in the different compartments of ASM cells. A PDGF-induced cytoplasmic calcium [Ca2+]C increase was attributed to both extracellular calcium influx and endoplasmic reticulum (ER) calcium [Ca2+]ER release, which was partially regulated by the PLC-IP3R pathway. Interestingly, the removal of the extracellular calcium influx led to inhibited ER calcium release, likely through inhibitory effects on the calcium-dependent activation of the ER ryanodine receptor. The inhibition of the L-type calcium channel on the plasma membrane or the SERCA pump on the ER resulted in both reduced [Ca2+]C and [Ca2+]ER from PDGF stimulation, while IP3R channel inhibition led to reduced [Ca2+]C only. The inhibited SERCA pump caused an immediate [Ca2+]C increase and [Ca2+]ER decrease, indicating active calcium exchange between the cytosol and ER storage in resting cells. PDGF-induced calcium at the outer mitochondrial membrane sub-region showed a similar regulatory response to cytosolic calcium, not influenced by the inhibition of the mitochondrial calcium uniporter channel. Therefore, our work identifies calcium flow pathways among the extracellular medium, cell cytosol, and ER via regulatory calcium channels. Specifically, extracellular calcium flow has an essential function in fully activating ER calcium release.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Crescimento Derivado de Plaquetas / Técnicas Biossensoriais / Cálcio / Miócitos de Músculo Liso / Transferência Ressonante de Energia de Fluorescência Limite: Humans Idioma: En Revista: Biosensors (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Crescimento Derivado de Plaquetas / Técnicas Biossensoriais / Cálcio / Miócitos de Músculo Liso / Transferência Ressonante de Energia de Fluorescência Limite: Humans Idioma: En Revista: Biosensors (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Suíça