PACS2 is required for ox-LDL-induced endothelial cell apoptosis by regulating mitochondria-associated ER membrane formation and mitochondrial Ca2+ elevation

Yu, Sanjiu; Zhang, Laiping; Liu, Chuan; Yang, Jie; Zhang, Jihang; Huang, Lan

doi:10.1016/j.yexcr.2019.04.002

Cited by 47 publications

(33 citation statements)

References 48 publications

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“…Similarly, increased MAM formation also participates in oxidized low-density lipoprotein (ox-LDL)induced EC apoptosis, the initial step of atherogenesis. Silencing a tethering protein in MAM, PACS2, inhibits ox-LDL-induced cell apoptosis, as well as concomitant mitochondrial Ca 2+ elevation, ROS production, and cytochrome c release (Yu et al, 2019). These findings confirm the importance of MAM in regulating endothelial function and participating in related vascular diseases.…”

Section: Vasculaturesupporting

confidence: 63%

Mitochondria-Associated Endoplasmic Reticulum Membranes in Cardiovascular Diseases

Gao

Yan

Zhu

2020

Front. Cell Dev. Biol.

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Section: Vasculaturesupporting

confidence: 63%

Mitochondria-Associated Endoplasmic Reticulum Membranes in Cardiovascular Diseases

Gao

Yan

Zhu

2020

Front. Cell Dev. Biol.

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“…2-APB, 2-aminoethoxydiphenyl borate; Ctrl, control; ECFC, endothelial colony-forming cell; ER, endoplasmic reticulum; InsP 3 Rs, inositol-1,4, 5-trisphosphate receptors; SE, standard error. *p < .05 membranes were recently reported in HUVECs (Yu et al, 2019). The Ca 2+ -dependent cross-talk between lysosomes and ER is largely interpreted within the framework of the "trigger hypothesis" originally put forward by Churchill and Galione (2001).…”

Section: The Acidic Ca 2+ Store Is Functionally Coupled To the Er Vmentioning

confidence: 87%

Nicotinic acid adenine dinucleotide phosphate activates two‐pore channel TPC1 to mediate lysosomal Ca²⁺ release in endothelial colony‐forming cells

Moccia

Zuccolo

Nezza

et al. 2020

Journal Cellular Physiology

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Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most recently discovered Ca 2+-releasing messenger that increases the intracellular Ca 2+ concentration by mobilizing the lysosomal Ca 2+ store through two-pore channels 1 (TPC1) and 2 (TPC2). NAADP-induced lysosomal Ca 2+ release regulates multiple endothelial functions, including nitric oxide release and proliferation. A sizeable acidic Ca 2+ pool endowed with TPC1 is also present in human endothelial colony-forming cells (ECFCs), which represent the only known truly endothelial precursors. Herein, we sought to explore the role of the lysosomal Ca 2+ store and TPC1 in circulating ECFCs by harnessing Ca 2+ imaging and molecular biology techniques. The lysosomotropic agent, Gly-Phe β-naphthylamide, and nigericin, which dissipates the proton gradient which drives Ca 2+ sequestration by acidic organelles, caused endogenous Ca 2+ release in the presence of a replete inositol-1,4,5-trisphosphate (InsP 3)sensitive endoplasmic reticulum (ER) Ca 2+ pool. Likewise, the amount of ER releasable Ca 2+ was reduced by disrupting lysosomal Ca 2+ content. Liposomal delivery of NAADP induced a transient Ca 2+ signal that was abolished by disrupting the lysosomal Ca 2+ store and by pharmacological and genetic blockade of TPC1. Pharmacological manipulation revealed that NAADP-induced Ca 2+ release also required ER-embedded InsP 3 receptors. Finally, NAADP-induced lysosomal Ca 2+ release was found to trigger vascular endothelial growth factor-induced intracellular Ca 2+ oscillations and proliferation, while it did not contribute to adenosine-5′trisphosphate-induced Ca 2+ signaling. These findings demonstrated that NAADPinduced TPC1-mediated Ca 2+ release can selectively be recruited to induce the Ca 2+ response to specific cues in circulating ECFCs.

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“…When 5-aminolevulinic acid mediated PDT is performed, Mfn2 expression was reduced, suggesting an production of endogenous ROS[ 41 ]. In addition, phosphofurin acidic cluster sorting protein 2 (PACS2) is an essential protein that mediates MAM-Ca 2+ overload[ 42 ]. PACS2 promotes the cleavage of BCR-associated protein(BAP)-31, which is an important factor in the caspase-8 apoptosis pathway activated by Ca 2+ .…”

Section: Production and Metabolism Of Ros During Pdtmentioning

confidence: 99%

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Zhang

Wang

et al. 2020

WJSC

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Photodynamic therapy (PDT) is an effective and promising cancer treatment. PDT directly generates reactive oxygen species (ROS) through photochemical reactions. This oxygen-dependent exogenous ROS has anti-cancer stem cell (CSC) effect. In addition, PDT may also increase ROS production by altering metabolism, endoplasmic reticulum stress, or potential of mitochondrial membrane. It is known that the half-life of ROS in PDT is short, with high reactivity and limited diffusion distance. Therefore, the main targeting position of PDT is often the subcellular localization of photosensitizers, which is helpful for us to explain how PDT affects CSC characteristics, including differentiation, self-renewal, apoptosis, autophagy, and immunogenicity. Broadly speaking, excess ROS will damage the redox system and cause oxidative damage to molecules such as DNA, change mitochondrial permeability, activate unfolded protein response, autophagy, and CSC resting state. Therefore, understanding the molecular mechanism by which ROS affect CSCs is beneficial to improve the efficiency of PDT and prevent tumor recurrence and metastasis. In this article, we review the effects of two types of photochemical reactions on PDT, the metabolic processes, and the biological effects of ROS in different subcellular locations on CSCs.

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PACS2 is required for ox-LDL-induced endothelial cell apoptosis by regulating mitochondria-associated ER membrane formation and mitochondrial Ca2+ elevation

Cited by 47 publications

References 48 publications

Mitochondria-Associated Endoplasmic Reticulum Membranes in Cardiovascular Diseases

Mitochondria-Associated Endoplasmic Reticulum Membranes in Cardiovascular Diseases

Nicotinic acid adenine dinucleotide phosphate activates two‐pore channel TPC1 to mediate lysosomal Ca²⁺ release in endothelial colony‐forming cells

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

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PACS2 is required for ox-LDL-induced endothelial cell apoptosis by regulating mitochondria-associated ER membrane formation and mitochondrial Ca2+ elevation

Cited by 47 publications

References 48 publications

Mitochondria-Associated Endoplasmic Reticulum Membranes in Cardiovascular Diseases

Mitochondria-Associated Endoplasmic Reticulum Membranes in Cardiovascular Diseases

Nicotinic acid adenine dinucleotide phosphate activates two‐pore channel TPC1 to mediate lysosomal Ca2+ release in endothelial colony‐forming cells

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

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Nicotinic acid adenine dinucleotide phosphate activates two‐pore channel TPC1 to mediate lysosomal Ca²⁺ release in endothelial colony‐forming cells