IP<sub>3</sub>Receptors, Mitochondria, and Ca<sup>2+</sup>Signaling: Implications for Aging

Decuypere, Jean-Paul; Monaco, Giovanni; Missiaen, Ludwig; Smedt, Humbert De; Parys, Jan B.; Bultynck, Geert

doi:10.4061/2011/920178

Cited by 94 publications

(71 citation statements)

References 211 publications

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“…One example is a ROS-mediated direct modification of inositol 1,4,5-trisphosphate (IP 3 ) receptor thiol groups that promotes Ca 2+ release from the endoplasmic reticulum [41]. ROS-mediated Ca 2+ regulation has been shown in osteoclast precursors during the differentiation process [39].…”

Section: Mapkmentioning

confidence: 99%

Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases

2015

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Osteoclasts are cells derived from bone marrow macrophages and are important in regulating bone resorption during bone homeostasis. Understanding what drives osteoclast differentiation and activity is important when studying diseases characterized by heightened bone resorption relative to formation, such as osteoporosis. In the last decade, studies have indicated that reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are crucial components that regulate the differentiation process of osteoclasts. However, there are still many unanswered questions that remain. This review will examine the mechanisms by which ROS can be produced in osteoclasts as well as how it may affect osteoclast differentiation and activity through its actions on osteoclastogenesis signaling pathways. In addition, the contribution of ROS to the aging-associated disease of osteoporosis will be addressed and how targeting ROS may lead to the development of novel therapeutic treatment options.

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Section: Mapkmentioning

confidence: 99%

Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases

2015

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“…17 These ubiquitously expressed channels control a wide range of cellular processes, including cell development, proliferation and death. [18][19][20][21] Downstream effects of intracellular Ca 2+ -release events depend on the spatiotemporal characteristics of the Ca 2+ signal. 22 Recently, it has been shown that knockdown or chemical inhibition of Ins(1,4,5) P 3 Rs, or depletion of Ins(1,4,5)P 3 induce autophagy.…”

Section: Introductionmentioning

confidence: 99%

Ins(1,4,5)P₃receptor-mediated Ca²⁺signaling and autophagy induction are interrelated

et al. 2011

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Immunoprecipitation experiments showed that during starvation Beclin 1, released from Bcl-2, first bound with increasing efficiency to Ins(1,4,5)P 3 Rs; after reaching a maximal binding after 3 h, binding, however, decreased again. The interaction site of Beclin 1 was determined to be present in the N-terminal Ins(1,4,5)P 3 -binding domain of the Ins(1,4,5) P 3 R. The starvation-induced Ins(1,4,5)P 3 R sensitization was abolished in cells treated with BECN1 siRNA, but not with ATG5 siRNA, pointing toward an essential role of Beclin 1 in this process. Moreover, recombinant Beclin 1 sensitized Ins(1,4,5) P 3 Rs in 45 Ca 2+ -flux assays, indicating a direct regulation of Ins(1,4,5)P 3 R activity by Beclin 1. Finally, we found that Ins(1,4,5) P 3 R-mediated Ca 2+ signaling was critical for starvation-induced autophagy stimulation, since the Ca 2+ chelator BAPTA-AM as well as the Ins(1,4,5)P 3 R inhibitor xestospongin B abolished the increase in LC3 lipidation and GFP-LC3-puncta formation. Hence, our results indicate a tight and essential interrelation between intracellular Ca 2+ signaling and autophagy stimulation as a proximal event in response to starvation.

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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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IP₃Receptors, Mitochondria, and Ca²⁺Signaling: Implications for Aging

Cited by 94 publications

References 211 publications

Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases

Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases

Ins(1,4,5)P₃receptor-mediated Ca²⁺signaling and autophagy induction are interrelated

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

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IP3Receptors, Mitochondria, and Ca2+Signaling: Implications for Aging

Cited by 94 publications

References 211 publications

Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases

Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases

Ins(1,4,5)P3receptor-mediated Ca2+signaling and autophagy induction are interrelated

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

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IP₃Receptors, Mitochondria, and Ca²⁺Signaling: Implications for Aging

Ins(1,4,5)P₃receptor-mediated Ca²⁺signaling and autophagy induction are interrelated