Bcl-2 binds to and inhibits ryanodine receptors

Vervliet, Tim; Decrock, Elke; Molgó, Jordi; Sorrentino, Vincenzo; Missiaen, Ludwig; Leybaert, Luc; Smedt, Humbert De; Kasri, Nael Nadif; Parys, Jan B.; Bultynck, Geert

doi:10.1242/jcs.150011

Cited by 56 publications

(61 citation statements)

References 76 publications

(94 reference statements)

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“…What is remarkable about these two signalling systems is the way they interact with each other [4] (figure 1 [9] and RYRs [10,11], is reduced by ROS [12]. ROS can activate a number of TRP channels that gate Ca 2þ (e.g.…”

Section: Integrated Calcium and Redox Signalling Pathwaysmentioning

confidence: 99%

Vitamin D, reactive oxygen species and calcium signalling in ageing and disease

Berridge¹

2016

Phil. Trans. R. Soc. B

102

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Section: Integrated Calcium and Redox Signalling Pathwaysmentioning

confidence: 99%

Vitamin D, reactive oxygen species and calcium signalling in ageing and disease

Berridge¹

2016

Phil. Trans. R. Soc. B

102

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“…Bcl-2 proteins have an N-terminal amino acid residue (K17) required for their interaction with IP3R to coordinate Calcium uptake into mitochondria to affect apoptosis [18][19][20]. There is recent evidence that the Na/K pump interacts with Bcl-2 proteins and thus with IP3R [21].…”

Section: In Vivo Administration Of As-mir-4262 Mimics the Effects Of mentioning

confidence: 99%

Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262

Hong

Gao²,

Xie

et al. 2015

Cell Physiol Biochem

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This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Abstract Background/Aims: Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI). The effects of ACE2 in ALI have been shown to not only result from its antagonizing hydrolyzing angiotensin II (AngII), which is responsible for reduction in the vascular tension and pulmonary accumulation of inflammatory cells, but also result from a role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells (PECs). Nevertheless, the underlying mechanisms of the role of ACE2 on PEC apoptosis are not completely understood. Methods: Here, we used a bleomycin-induced mouse model for ALI that has been published in our previous studies. We analyzed the mRNA and protein levels of an anti-apoptotic protein Bcl-2 in the ALI-mice that have been treated w/o ACE2. We analyzed miR-4262 levels in the mouse lung in these mice. Bcl-2-targeting miRNAs were predicted using bioinformatics algorithms and a luciferase reporter assay was applied to examine the effects of miR-4262 on the Bcl-2 protein translation upon their binding to 3'-UTR of Bcl-2 mRNA. Adeno-associated viruses carrying either miR-4262 mimics or antisense were injected into ALI-mice without ACE2, and their effects on the apoptosis in mouse lung cells were analyzed by Western blot. Results: ACE2 inhibited the ALI-induced apoptosis of pulmonary cells in vivo partially through upregulation of Bcl-2 protein, but not Bcl-2 mRNA. ACE2 appeared to significantly suppress the upregulation of miR-4262 in mouse lung after ALI. MiR-4262 was found to target 3'-UTR of Bcl-2 mRNA to inhibit its protein translation in PECs. In vivo administration of antisense of miR-4262 decreased apoptosis of pulmonary cells and severity of the ALI in mice. Conclusion: ACE2-induced suppression of miR-4262 partially contribute to the inhibition of the PEC apoptosis after ALI through Bcl-2. MiR-4262 may be a novel promising treatment target for ALI and ARDS.

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“…Bcl-2 directly targets different Ca 2+ -flux systems, including intracellular Ca 2+ -release channels [21,22]. As such, Bcl-2 can directly bind to inositol 1,4,5-trisphosphate receptors (IP 3 Rs), thereby suppressing pro-apoptotic Ca 2+ fluxes from the ER [21,23].…”

Section: Introductionmentioning

confidence: 99%