Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Oflaz, FE; Koshenov, Z; Hirtl, M; Rost, R; Bachkoenig, OA; Gottschalk, B; Madreiter-Sokolowski, CT; Malli, R; Graier, WF.
Near-UV Light Induced ROS Production Initiates Spatial Ca²⁺ Spiking to Fire NFATc3 Translocation.
Int J Mol Sci. 2021; 22(15): 8189 Doi: 10.3390/ijms22158189 [OPEN ACCESS]
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Leading authors Med Uni Graz

Graier Wolfgang

Oflaz Furkan Enes

Co-authors Med Uni Graz

Bachkönig Olaf Arne Georg

Gottschalk Benjamin

Hirtl Martin

Koshenov Zhanat

Madreiter-Sokolowski Corina

Malli Roland

Rost René

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Abstract:

Ca²⁺-dependent gene regulation controls several functions to determine the fate of the cells. Proteins of the nuclear factor of activated T-cells (NFAT) family are Ca²⁺ sensitive transcription factors that control the cell growth, proliferation and insulin secretion in β-cells. Translocation of NFAT proteins to the nucleus occurs in a sequence of events that starts with activating calmodulin-dependent phosphatase calcineurin in a Ca²⁺-dependent manner, which dephosphorylates the NFAT proteins and leads to their translocation to the nucleus. Here, we examined the role of IP₃-generating agonists and near-UV light in the induction of NFATc3 migration to the nucleus in the pancreatic β-cell line INS-1. Our results show that IP₃ generation yields cytosolic Ca²⁺ rise and NFATc3 translocation. Moreover, near-UV light exposure generates reactive oxygen species (ROS), resulting in cytosolic Ca²⁺ spiking via the L-type Ca²⁺ channel and triggers NFATc3 translocation to the nucleus. Using the mitochondria as a Ca²⁺ buffering tool, we showed that ROS-induced cytosolic Ca²⁺ spiking, not the ROS themselves, was the triggering mechanism of nuclear import of NFATc3. Collectively, this study reveals the mechanism of near-UV light induced NFATc3 migration.

Find related publications in this database (Keywords)

UV light

ROS

L-type Ca2+ channel

transcription factor

NFATc3 translocation

mitochondrial Ca2+ buffering

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