Pigment epithelium-derived factor hinders photoreceptor cell death by reducing intracellular calcium in the degenerating retina.

Abstract:

:Calcium ions play a critical role in neuronal cell death. Pigment epithelium-derived factor (PEDF) is a promising neuroprotective protein for photoreceptor cells but the mechanisms mediating its effects against retinal degeneration are still not well characterized. We addressed this question in the rd1 degenerating mouse retina that bears a mutation in the Pde6b gene encoding one subunit of the phosphodiesterase enzyme. Loss of phosphodiesterase activity in rod photoreceptor cells increases cyclic guanosine monophosphate (cGMP) levels leading to a rise in intracellular calcium. Short-term treatments with recombinant human PEDF protein decreased intracellular calcium in photoreceptors in vivo. Taking advantage of calcium pump blockers, we defined that PEDF signaling acts on PMCA calcium pumps to lower intracellular calcium. PEDF restrained cell death pathways activated by high calcium levels and engaging calpains, BAX and AIF. The neurotrophic effects were mediated by the PEDF receptor (PEDF-R), encoded by the PNPLA2 gene. Finally, peptides containing the neurotrophic domain of PEDF targeted these same cell death pathways in vivo. The findings reveal rescue from death of degenerating photoreceptor cells by a PEDF-mediated preservation of intracellular calcium homeostasis.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Comitato A,Subramanian P,Turchiano G,Montanari M,Becerra SP,Marigo V

doi

10.1038/s41419-018-0613-y

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

560

issue

5

issn

2041-4889

pii

10.1038/s41419-018-0613-y

journal_volume

9

pub_type

杂志文章
  • p53 cooperates with SIRT6 to regulate cardiolipin de novo biosynthesis.

    abstract::The tumor suppressor p53 has critical roles in regulating lipid metabolism, but whether and how p53 regulates cardiolipin (CL) de novo biosynthesis is unknown. Here, we report that p53 physically interacts with histone deacetylase SIRT6 in vitro and in vivo, and this interaction increases following palmitic acid (PA) ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0984-0

    authors: Li M,Hou T,Gao T,Lu X,Yang Q,Zhu Q,Li Z,Liu C,Mu G,Liu G,Bao Y,Wen H,Wang L,Wang H,Zhao Y,Gu W,Yang Y,Zhu WG

    更新日期:2018-09-20 00:00:00

  • Rapamycin reverses insulin resistance (IR) in high-glucose medium without causing IR in normoglycemic medium.

    abstract::Mammalian target of rapamycin (mTOR) is involved in insulin resistance (IR) and diabetic retinopathy. In retinal pigment epithelial (RPE) cells, insulin activates the mTOR pathway, inducing hypoxia-inducible factor-1α (HIF-1α) and HIF-dependent transcription in serum-free minimum essential medium Eagle (MEM). Serendip...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.178

    authors: Leontieva OV,Demidenko ZN,Blagosklonny MV

    更新日期:2014-05-08 00:00:00

  • Long noncoding RNA SNHG14 facilitates colorectal cancer metastasis through targeting EZH2-regulated EPHA7.

    abstract::Accumulating evidence suggested the participation of long noncoding RNAs (lncRNAs) in regulating various biological processes so as to affecting cancer progression. However, the functional role of most lncRNAs in colorectal carcer (CRC) is still largely covered. In the present study, we disclosed SNHG14 as a carcinoge...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1707-x

    authors: Di W,Weinan X,Xin L,Zhiwei Y,Xinyue G,Jinxue T,Mingqi L

    更新日期:2019-07-04 00:00:00

  • Chloride channels are necessary for full platelet phosphatidylserine exposure and procoagulant activity.

    abstract::Platelets enhance thrombin generation at sites of vascular injury by exposing phosphatidylserine during necrosis-like cell death. Anoctamin 6 (Ano6) is required for Ca(2+)-dependent phosphatidylserine exposure and is defective in patients with Scott syndrome, a rare bleeding disorder. Ano6 may also form Cl(-) channels...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.495

    authors: Harper MT,Poole AW

    更新日期:2013-12-19 00:00:00

  • Echinatin suppresses esophageal cancer tumor growth and invasion through inducing AKT/mTOR-dependent autophagy and apoptosis.

    abstract::Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor survival. It is urgent to search for new efficient drugs with good stability and safety for clinical therapy. This study aims to identify potential anticancer drugs from a compound library consisting of 429 natural products....

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2730-7

    authors: Hong P,Liu QW,Xie Y,Zhang QH,Liao L,He QY,Li B,Xu WW

    更新日期:2020-07-13 00:00:00

  • MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro.

    abstract::Providing a conducive microenvironment is critical to increase survival of transplanted stem cells in regenerative therapy. Hyperglycemia promotes stem cell death impairing cardiac regeneration in the diabetic heart. Understanding the molecular mechanisms of high glucose-induced stem cell death is important for improv...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2367-6

    authors: Yadav SK,Kambis TN,Kar S,Park SY,Mishra PK

    更新日期:2020-03-13 00:00:00

  • MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1.

    abstract::MicroRNAs (miRNAs) have been demonstrated to affect the biological processes of cancers and showed great potential for prognostic biomarkers. In this study, we screened differentially expressed miRNAs in ccRCC based on three dimensions of metastasis, prognosis, and differential expression compared to normal tissue usi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03306-y

    authors: Li Z,Zhao S,Zhu S,Fan Y

    更新日期:2021-01-04 00:00:00

  • Ca2+-dependent recruitment of voltage-gated sodium channels underlies bilirubin-induced overexcitation and neurotoxicity.

    abstract::Neonatal jaundice is prevalent among newborns and can lead to severe neurological deficits, particularly sensorimotor dysfunction. Previous studies have shown that bilirubin (BIL) enhances the intrinsic excitability of central neurons and this can potentially contribute to their overexcitation, Ca2+ overload, and neur...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1979-1

    authors: Shi HS,Lai K,Yin XL,Liang M,Ye HB,Shi HB,Wang LY,Yin SK

    更新日期:2019-10-10 00:00:00

  • Combined reduction in the expression of MCL-1 and BCL-2 reduces organismal size in mice.

    abstract::The intrinsic apoptotic pathway is controlled by the BCL-2 family of proteins, which exhibit either a pro-death or pro-survival function. Gene knockout studies revealed that different pro-survival BCL-2 proteins are critical for the survival of distinct cell types, although overlapping functions amongst such proteins ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2376-5

    authors: Ke F,Lancaster GI,Grabow S,Murphy AJ,Strasser A

    更新日期:2020-03-13 00:00:00

  • The ATF6 branch of unfolded protein response and apoptosis are activated to promote African swine fever virus infection.

    abstract::African swine fever virus (ASFV) infection induces apoptosis in the infected cell; however, the consequences of this activation on virus replication have not been defined. In order to identify the role of apoptosis in ASFV infection, we analyzed caspase induction during the infection and the impact of caspase inhibiti...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.81

    authors: Galindo I,Hernáez B,Muñoz-Moreno R,Cuesta-Geijo MA,Dalmau-Mena I,Alonso C

    更新日期:2012-07-05 00:00:00

  • Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification.

    abstract::Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we conf...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.519

    authors: Xu X,Yin Y,Tang J,Xie Y,Han Z,Zhang X,Liu Q,Qin X,Huang X,Sun B

    更新日期:2017-10-12 00:00:00

  • BMP2 sensitizes glioblastoma stem-like cells to Temozolomide by affecting HIF-1α stability and MGMT expression.

    abstract::Glioblastoma multiforme (GBM) is the most common brain tumour, characterized by a central and partially necrotic (i.e., hypoxic) core enriched in cancer stem cells (CSCs). We previously showed that the most hypoxic and immature (i.e., CSCs) GBM cells were resistant to Temozolomide (TMZ) in vitro, owing to a particular...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.153

    authors: Persano L,Pistollato F,Rampazzo E,Della Puppa A,Abbadi S,Frasson C,Volpin F,Indraccolo S,Scienza R,Basso G

    更新日期:2012-10-18 00:00:00

  • Serum amyloid A inhibits dendritic cell apoptosis to induce glucocorticoid resistance in CD4(+) T cells.

    abstract::Mediators produced by the airway epithelium control the activation, recruitment, and survival of pulmonary dendritic cells (DC) that present antigen to CD4(+) T cells during the genesis and exacerbation of allergic asthma. The epithelial-derived acute phase protein, serum amyloid A (SAA), induces DC maturation and TH1...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.327

    authors: Ather JL,Fortner KA,Budd RC,Anathy V,Poynter ME

    更新日期:2013-09-05 00:00:00

  • TXNIP regulates mitophagy in retinal Müller cells under high-glucose conditions: implications for diabetic retinopathy.

    abstract::Thioredoxin-interacting protein (TXNIP) is involved in oxidative stress and apoptosis in diabetic retinopathy. However, the role of TXNIP in the removal of damaged mitochondria (MT) via mitophagy, a process of macroautophagy, remains unexplored. Here we investigate the associated cellular and molecular mechanisms unde...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.190

    authors: Devi TS,Somayajulu M,Kowluru RA,Singh LP

    更新日期:2017-05-11 00:00:00

  • Upregulation of IGF2R evades lysosomal dysfunction-induced apoptosis of cervical cancer cells via transport of cathepsins.

    abstract::Cervical cancer is the most common gynecological malignancy in the world; however, the survival rates of advanced-stage and recurrent cervical cancer patients remain poor. The multifaced protein insulin-like growth factor 2 receptor (IGF2R) has various ligands, represented as IGF-2 and mannose-6-phosphate (M6P)-tagged...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2117-9

    authors: Takeda T,Komatsu M,Chiwaki F,Komatsuzaki R,Nakamura K,Tsuji K,Kobayashi Y,Tominaga E,Ono M,Banno K,Aoki D,Sasaki H

    更新日期:2019-11-20 00:00:00

  • Inhibition of thyroid hormone signaling protects retinal pigment epithelium and photoreceptors from cell death in a mouse model of age-related macular degeneration.

    abstract::Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Dry AMD is characterized by a progressive macular degeneration of the retinal pigment epithelium (RPE) and photoreceptors, and the RPE oxidative damage/dystrophy is at the core of the disease. Recent population/patients-based stud...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2216-7

    authors: Ma H,Yang F,Ding XQ

    更新日期:2020-01-13 00:00:00

  • MicroRNA-302 induces proliferation and inhibits oxidant-induced cell death in human adipose tissue-derived mesenchymal stem cells.

    abstract::Mesenchymal stem cells (MSCs) are a heterogeneous population of cells that proliferate in vitro as plastic-adherent cells, have a fibroblast-like morphology, form colonies in vitro and can differentiate into bone, cartilage and fat cells. The abundance, ease and repeatable access to subcutaneous adipose tissue and the...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.344

    authors: Kim JY,Shin KK,Lee AL,Kim YS,Park HJ,Park YK,Bae YC,Jung JS

    更新日期:2014-08-21 00:00:00

  • Correction: Schwann cells support oncogenic potential of pancreatic cancer cells through TGFβ signaling.

    abstract::The original version of this article contained an error in the name of one of the co-authors (Kayvan Mohkam). This has been corrected in the PDF and HTML versions. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-020-2262-1

    authors: Roger E,Martel S,Bertrand-Chapel A,Depollier A,Chuvin N,Pommier RM,Yacoub K,Caligaris C,Cardot-Ruffino V,Chauvet V,Aires S,Mohkam K,Mabrut JY,Adham M,Fenouil T,Hervieu V,Broutier L,Castets M,Neuzillet C,Cassier PA,

    更新日期:2020-01-23 00:00:00

  • Dissecting cell diversity and connectivity in skeletal muscle for myogenesis.

    abstract::Characterized by their slow adhering property, skeletal muscle myogenic progenitor cells (MPCs) have been widely utilized in skeletal muscle tissue engineering for muscle regeneration, but with limited efficacy. Skeletal muscle regeneration is regulated by various cell types, including a large number of rapidly adheri...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1647-5

    authors: Liu YX,Wu BB,Gong L,An CR,Lin JX,Li QK,Jiang DM,Jin KX,Mechakra A,Bunpetch V,Li Y,Zou YW,Ouyang HW,Zou XH

    更新日期:2019-06-03 00:00:00

  • Phlpp1 is associated with human intervertebral disc degeneration and its deficiency promotes healing after needle puncture injury in mice.

    abstract::Back pain is a leading cause of global disability and is strongly associated with intervertebral disc (IVD) degeneration (IDD). Hallmarks of IDD include progressive cell loss and matrix degradation. The Akt signaling pathway regulates cellularity and matrix production in IVDs and its inactivation is known to contribut...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1985-3

    authors: Zhang C,Smith MP,Zhou GK,Lai A,Hoy RC,Mroz V,Torre OM,Laudier DM,Bradley EW,Westendorf JJ,Iatridis JC,Illien-Jünger S

    更新日期:2019-10-03 00:00:00

  • MiR203 mediates subversion of stem cell properties during mammary epithelial differentiation via repression of ΔNP63α and promotes mesenchymal-to-epithelial transition.

    abstract::During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, i...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.37

    authors: DeCastro AJ,Dunphy KA,Hutchinson J,Balboni AL,Cherukuri P,Jerry DJ,DiRenzo J

    更新日期:2013-02-28 00:00:00

  • How cell death shapes cancer.

    abstract::Apoptosis has been established as a mechanism of anti-cancer defense. Members of the BCL-2 family are critical mediators of apoptotic cell death in health and disease, often found to be deregulated in cancer and believed to lead to the survival of malignant clones. However, over the years, a number of studies pointed ...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2015.20

    authors: Labi V,Erlacher M

    更新日期:2015-03-05 00:00:00

  • Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine model of aortic aneurysm.

    abstract::Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechan...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.88

    authors: Ang LS,Boivin WA,Williams SJ,Zhao H,Abraham T,Carmine-Simmen K,McManus BM,Bleackley RC,Granville DJ

    更新日期:2011-09-08 00:00:00

  • Prolyl hydroxylase 2 silencing enhances the paracrine effects of mesenchymal stem cells on necrotizing enterocolitis in an NF-κB-dependent mechanism.

    abstract::Treatment options for necrotizing enterocolitis (NEC) remain inadequate. Here we examined if and how prolyl hydroxylase 2 (PHD2) silencing enhances the paracrine effects of bone-marrow-derived mesenchymal stem cells (BM-MSCs) on NEC. In this study, BM-MSCs were transduced with lentiviruses containing GFP (GFP-MSC) or ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2378-3

    authors: Chen H,Zhang H,Zheng Y,Min X,Luo Y,Zhou W,Ma F,Li J,Lu Q,Zhang C,Cai H,Sha W

    更新日期:2020-03-16 00:00:00

  • Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress.

    abstract::Japanese encephalitis virus (JEV), which is a causative agent of sporadic encephalitis, harbours itself inside the neural stem/progenitor cells. It is a well-known fact that JEV infects neural stem/progenitor cells and decreases their proliferation capacity. With mass spectrometry-based quantitative proteomic study, i...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.394

    authors: Mukherjee S,Singh N,Sengupta N,Fatima M,Seth P,Mahadevan A,Shankar SK,Bhattacharyya A,Basu A

    更新日期:2017-01-19 00:00:00

  • Glucolipotoxicity initiates pancreatic β-cell death through TNFR5/CD40-mediated STAT1 and NF-κB activation.

    abstract::Type 2 diabetes is a chronic metabolic disorder, where failure to maintain normal glucose homoeostasis is associated with, and exacerbated by, obesity and the concomitant-elevated free fatty acid concentrations typically found in these patients. Hyperglycaemia and hyperlipidaemia together contribute to a decline in in...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.203

    authors: Bagnati M,Ogunkolade BW,Marshall C,Tucci C,Hanna K,Jones TA,Bugliani M,Nedjai B,Caton PW,Kieswich J,Yaqoob MM,Ball GR,Marchetti P,Hitman GA,Turner MD

    更新日期:2016-08-11 00:00:00

  • Wnt3a disrupts GR-TEAD4-PPARγ2 positive circuits and cytoskeletal rearrangement in a β-catenin-dependent manner during early adipogenesis.

    abstract::Adipogenesis is a process which induces or represses many genes in a way to drive irreversible changes of cell phenotypes; lipid accumulation, round cell-shape, secreting many adipokines. As a master transcription factor (TF), PPARγ2 induces several target genes to orchestrate these adipogenic changes. Thus induction ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1249-7

    authors: Park B,Chang S,Lee GJ,Kang B,Kim JK,Park H

    更新日期:2019-01-08 00:00:00

  • Overaccumulation of p53-mediated autophagy protects against betulinic acid-induced apoptotic cell death in colorectal cancer cells.

    abstract::Betulinic acid (BA) exhibits cytotoxic activity against some cancer cells. However, the molecular mechanism of BA against CRC cells was little reported. Here, we proved that BA elicited CRC cells' growth inhibition and apoptosis in a dose-dependent manner. In addition, BA treatment induced autophagy via inhibiting the...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.485

    authors: Wang S,Wang K,Zhang C,Zhang W,Xu Q,Wang Y,Zhang Y,Li Y,Zhang Y,Zhu H,Song F,Lei Y,Bu Y

    更新日期:2017-10-05 00:00:00

  • Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma.

    abstract::Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinosta...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.306

    authors: Matthews GM,Lefebure M,Doyle MA,Shortt J,Ellul J,Chesi M,Banks KM,Vidacs E,Faulkner D,Atadja P,Bergsagel PL,Johnstone RW

    更新日期:2013-09-12 00:00:00

  • Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells.

    abstract::Patients with high-grade serous ovarian cancer (HGSC) frequently receive platinum-based chemotherapeutics, such as cisplatin. Cisplatin binds to DNA and induces DNA-damage culminating in mitochondria-mediated apoptosis. Interestingly, mitochondrial DNA is critically affected by cisplatin but its relevance in cell deat...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2081-4

    authors: Kleih M,Böpple K,Dong M,Gaißler A,Heine S,Olayioye MA,Aulitzky WE,Essmann F

    更新日期:2019-11-07 00:00:00