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The effects of CypA on apoptosis: potential target for the treatment of diseases

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Abstract

Cyclophilin A (CypA), the first member of cyclophilins, is distributed extensively in eukaryotic and prokaryotic cells, primarily localized in the cytoplasm. In addition to acting as an intracellular receptor for cyclosporin A (CSA), CypA plays a crucial role in diseases such as aging and tumorigenesis. Apoptosis, a form of programmed cell death, is able to balance the rate of cell viability and death. In this review, we focus on the effects of CypA on apoptosis and the relationship between specific mechanisms of CypA promoting or inhibiting apoptosis and diseases, including tumorigenesis, cardiovascular diseases, organ injury, and microbial infections. Notably, the process of CypA promoting or inhibiting apoptosis is closely related to disease development. Finally, future prospects for the association of CypA and apoptosis are discussed, and a comprehensive understanding of the effects of CypA on apoptosis in relation to diseases is expected to provide new insights into the design of CypA as a therapeutic target for diseases.

Key points

• Understand the effect of CypA on apoptosis.

• CypA affects apoptosis through specific pathways.

• The effect of CypA on apoptosis is associated with a variety of disease processes.

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References

  • Ahmed F, Yao XQ, Hamelberg D (2023) Conserved conformational dynamics reveal a key dynamic residue in the gatekeeper loop of human cyclophilins. J Phys Chem B 127:3139–3150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bauer K, Kretzschmar AK, Cvijic H, Blumert C, Loeffler D, Brocke-Heidrich K, Schiene-Fischer C, Fischer G, Sinz A, Clevenger CV, Horn F (2009) Cyclophilins contribute to Stat3 signaling and survival of multiple myeloma cells. Oncogene 28:2784–2795

    Article  CAS  PubMed  Google Scholar 

  • Bonfils C, Bec N, Larroque C, Del Rio M, Gongora C, Pugnière M, Martineau P (2010) Cyclophilin A as negative regulator of apoptosis by sequestering cytochrome c. Biochem Biophys Res Commun 393:325–330

    Article  CAS  PubMed  Google Scholar 

  • Cabello R, Fontecha-Barriuso M, Martin-Sanchez D, Lopez-Diaz AM, Carrasco S, Mahillo I, Gonzalez-Enguita C, Sanchez-Niño MD, Ortiz A, Sanz AB (2021a) Urinary cyclophilin A as marker of tubular cell death and kidney injury. Biomedicines 9:217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Candé C, Vahsen N, Kouranti I, Schmitt E, Daugas E, Spahr C, Luban J, Kroemer RT, Giordanetto F, Garrido C, Penninger JM, Kroemer G (2004) AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis. Oncogene 23:1514–1521

    Article  PubMed  Google Scholar 

  • Chen S, Zhang M, Ma H, Saiyin H, Shen S, Xi J, Wan B, Yu L (2008) Oligo-microarray analysis reveals the role of cyclophilin A in drug resistance. Cancer Chemother Pharmacol 61:459–469

    Article  CAS  PubMed  Google Scholar 

  • Cheng F, Yuan W, Cao M, Chen R, Wu X, Yan J (2019) Cyclophilin A protects cardiomyocytes against hypoxia/reoxygenation-induced apoptosis via the AKT/Nox2 pathway. Oxid Med Cell Longev 2019:2717986

    Article  PubMed  PubMed Central  Google Scholar 

  • Cho HJ, Jung HJ (2023) Cyclophilin A inhibitors suppress proliferation and induce apoptosis of MKN45 gastric cancer stem-like cells by regulating CypA/CD147-mediated signaling pathway. Int J Mol Sci 24:4734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi KJ, Piao YJ, Lim MJ, Kim JH, Ha J, Choe W, Kim SS (2007) Overexpressed cyclophilin A in cancer cells renders resistance to hypoxia- and cisplatin-induced cell death. Cancer Res 67:3654–3662

    Article  CAS  PubMed  Google Scholar 

  • Conte M, Palumbo R, Monti A, Fontana E, Nebbioso A, Ruvo M, Altucci L, Doti N (2021) Relevance of AIF/CypA lethal pathway in SH-SY5Y cells treated with staurosporine. Int J Mol Sci 23:265

    Article  PubMed  PubMed Central  Google Scholar 

  • Daneri-Becerra C, Valeiras B, Gallo LI, Lagadari M, Galigniana MD (2021) Cyclophilin A is a mitochondrial factor that forms complexes with p23 — correlative evidence for an anti-apoptotic action. J Cell Sci 134:jcs253401

    Article  CAS  PubMed  Google Scholar 

  • Dear JW, Simpson KJ, Nicolai MP, Catterson JH, Street J, Huizinga T, Craig DG, Dhaliwal K, Webb S, Bateman DN, Webb DJ (2011) Cyclophilin A is a damage-associated molecular pattern molecule that mediates acetaminophen-induced liver injury. J Immunol 187:3347–3352

    Article  CAS  PubMed  Google Scholar 

  • Doti N, Reuther C, Scognamiglio PL, Dolga AM, Plesnila N, Ruvo M, Culmsee C (2014) Inhibition of the AIF/CypA complex protects against intrinsic death pathways induced by oxidative stress. Cell Death Dis 5:e993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doti N, Ruvo M (2017) Relevance and therapeutic potential of CypA targeting to block apoptosis inducing factor-mediated neuronal cell death. Neural Regen Res 12:1428–1429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan J, Fan Y, Wang X, Niu L, Duan L, Yang J, Li L, Gao Y, Wu X, Luo C (2019) PLCε regulates prostate cancer mitochondrial oxidative metabolism and migration via upregulation of Twist1. J Exp Clin Cancer Res 38:337

    Article  PubMed  PubMed Central  Google Scholar 

  • Feng J, Meng W, Chen L, Zhang X, Markazi A, Yuan W, Huang Y, Gao SJ (2023) N(6)-methyladenosine and reader protein YTHDF2 enhance the innate immune response by mediating DUSP1 mRNA degradation and activating mitogen-activated protein kinases during bacterial and viral infections. mBio 14:e0334922

    Article  PubMed  Google Scholar 

  • Gegunde S, Alfonso A, Alvariño R, Pérez-Fuentes N, Bayón-Lorenzo J, Alonso E, Ocaranza-Sánchez R, Abellás-Sequeiros RA, Santás-Álvarez M, Vieytes MR, Juanatey-González C, Botana LM (2023) Association of cyclophilins and cardiovascular risk factors in coronary artery disease. Front Physiol 14:1127468

    Article  PubMed  PubMed Central  Google Scholar 

  • Gong A, Wang X, Wang X, Zhao Y, Cui Y (2023) Twist1 promoter methylation regulates the proliferation and apoptosis of acute myeloid leukemia cells via PI3K/AKT pathway. Indian J Hematol Blood Transfus 39:25–32

    Article  PubMed  Google Scholar 

  • Gorry R, Brennan K, Lavin PT, Sheridan R, Mc Gee MM (2023) Phosphorylation of the prolyl isomerase cyclophilin A regulates its localisation and release from the centrosome during mitosis. Cell Cycle 22:951–966

    Article  CAS  PubMed  Google Scholar 

  • Han JM, Sohng JK, Lee WH, Oh TJ, Jung HJ (2021) Identification of Cyclophilin A as a potential anticancer target of novel nargenicin A1 analog in AGS gastric cancer cells. Int J Mol Sci 22:2473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong J, Zhou J, Fu J, He T, Qin J, Wang L, Liao L, Xu J (2011) Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness. Cancer Res 71:3980–3990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howard BA, Furumai R, Campa MJ, Rabbani ZN, Vujaskovic Z, Wang XF, Patz EF Jr (2005) Stable RNA interference-mediated suppression of cyclophilin A diminishes non-small-cell lung tumor growth in vivo. Cancer Res 65:8853–8860

    Article  CAS  PubMed  Google Scholar 

  • Izadi S, Najfizadeh SR, Nejati A, TeimooriRad M, Shahmahmoodi S, Shirazi FG, Shokri F, Marashi SM (2023) Potential role of EBV and toll-like receptor 9 ligand in patients with systemic lupus erythematosus. Immunol Res 71(5):698–708. https://doi.org/10.1007/s12026-023-09380-6

    Article  CAS  PubMed  Google Scholar 

  • Jiang B, Zhou X, Yang T, Wang L, Feng L, Wang Z, Xu J, Jing W, Wang T, Su H, Yang G, Zhang Z (2023) The role of autophagy in cardiovascular disease: cross-interference of signaling pathways and underlying therapeutic targets. Front Cardiovasc Med 10:1088575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang X, Zhang QL, Tian YH, Huang JC, Ma GL (2017) RNA interference-mediated gene silencing of cyclophilin A enhances the radiosensitivity of PAa human lung adenocarcinoma cells in vitro. Oncol Lett 13:1619–1624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim H, Oh Y, Kim K, Jeong S, Chon S, Kim D, Jung MH, Pak YK, Ha J, Kang I, Choe W (2015) Cyclophilin A regulates JNK/p38-MAPK signaling through its physical interaction with ASK1. Biochem Biophys Res Commun 464:112–117

    Article  CAS  PubMed  Google Scholar 

  • Kim SH, Lessner SM, Sakurai Y, Galis ZS (2004) Cyclophilin A as a novel biphasic mediator of endothelial activation and dysfunction. Am J Pathol 164:1567–1574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Labuschagne CF, Cheung EC, Blagih J, Domart MC, Vousden KH (2019) Cell clustering promotes a metabolic switch that supports metastatic colonization. Cell Metab 30:720–34.e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lahaye X, Satoh T, Gentili M, Cerboni S, Silvin A, Conrad C, Ahmed-Belkacem A, Rodriguez EC, Guichou JF, Bosquet N, Piel M, Le Grand R, King MC, Pawlotsky JM, Manel N (2016) Nuclear envelope protein SUN2 promotes cyclophilin-A-dependent steps of HIV replication. Cell Rep 15:879–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lassègue B, San Martín A, Griendling KK (2012) Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 110:1364–1390

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee J (2010) Novel combinational treatment of cisplatin with cyclophilin A inhibitors in human heptocellular carcinomas. Arch Pharm Res 33:1401–1409

    Article  CAS  PubMed  Google Scholar 

  • Lee SP, Hwang YS, Kim YJ, Kwon KS, Kim HJ, Kim K, Chae HZ (2001) Cyclophilin a binds to peroxiredoxins and activates its peroxidase activity. J Biol Chem 276:29826–29832

    Article  CAS  PubMed  Google Scholar 

  • Li AL, Li HY, Jin BF, Ye QN, Zhou T, Yu XD, Pan X, Man JH, He K, Yu M, Hu MR, Wang J, Yang SC, Shen BF, Zhang XM (2004) A novel eIF5A complex functions as a regulator of p53 and p53-dependent apoptosis. J Biol Chem 279:49251–49258

    Article  CAS  PubMed  Google Scholar 

  • Li L, Tang W, Wu X, Karnak D, Meng X, Thompson R, Hao X, Li Y, Qiao XT, Lin J, Fuchs J, Simeone DM, Chen ZN, Lawrence TS, Xu L (2013b) HAb18G/CD147 promotes pSTAT3-mediated pancreatic cancer development via CD44s. Clin Cancer Res 19:6703–6715

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Min W, Gou J (2013a) Knockdown of cyclophilin A reverses paclitaxel resistance in human endometrial cancer cells via suppression of MAPK kinase pathways. Cancer Chemother Pharmacol 72:1001–1011

    Article  CAS  PubMed  Google Scholar 

  • Liao Y, Luo D, Peng K, Zeng Y (2021) Cyclophilin A: a key player for etiological agent infection. Appl Microbiol Biotechnol 105:1365–1377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liao Y, Peng K, Li X, Ye Y, Liu P, Zeng Y (2022) The adhesion protein of Mycoplasma genitalium inhibits urethral epithelial cell apoptosis through CypA-CD147 activating PI3K/ Akt/NF-κB pathway. Appl Microbiol Biotechnol 106:6657–6669

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Guo M, Lv Z, Wang Z, Shao Y, Li C (2020a) A cyclophilin A (CypA) from Apostichopus japonicus modulates NF-κB translocation as a cofactor. Fish Shellfish Immunol 98:728–737

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Zhao X, Lv Z, Guo M, Li C (2020b) Cyclophilin A mediates coelomocyte apoptosis via the NF-κB/Bcl-2 signaling pathway in Apostichopus japonicus. Dev Comp Immunol 107:103657

    Article  CAS  PubMed  Google Scholar 

  • Liu W, Zhang Q, Zhang Y, Sun L, Xiao H, Luo B (2023) Epstein-Barr virus regulates endothelin-1 expression through the ERK/FOXO1 pathway in EBV-associated gastric cancer. Microbiol Spectr 11:e0089822

    Article  PubMed  Google Scholar 

  • Liu X, Sun L, Yu M, Wang Z, Xu C, Xue Q, Zhang K, Ye X, Kitamura Y, Liu W (2009) Cyclophilin A interacts with influenza A virus M1 protein and impairs the early stage of the viral replication. Cell Microbiol 11:730–741

    Article  CAS  PubMed  Google Scholar 

  • Lu T, Aron L, Zullo J, Pan Y, Kim H, Chen Y, Yang T-H, Kim H-M, Derek Drake X, Liu S, Bennett DA, Colaiacovo MP, Yankner BA (2016) REST and stress resistance in ageing and Alzheimer’s disease (vol 507, pg 448, 2014). Nature 540:448–454

    Google Scholar 

  • Lu W, Cheng F, Yan W, Li X, Yao X, Song W, Liu M, Shen X, Jiang H, Chen J, Li J, Huang J (2017) Selective targeting p53(WT) lung cancer cells harboring homozygous p53 Arg72 by an inhibitor of CypA. Oncogene 36:4719–4731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo YR, Kudo TA, Tominami K, Izumi S, Tanaka T, Hayashi Y, Noguchi T, Matsuzawa A, Nakai J, Hong G, Wang H (2022) SP600125 enhances temperature-controlled repeated thermal stimulation-induced neurite outgrowth in PC12-P1F1 cells. Int J Mol Sci 23:15602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma Z, Zhang W, Wu Y, Zhang M, Wang L, Wang Y, Wang Y, Liu W (2021) Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway. Biosci Rep 41:BSR20203219

    Article  PubMed  PubMed Central  Google Scholar 

  • Mamatis JE, Pellizzari-Delano IE, Gallardo-Flores CE, Colpitts CC (2022) Emerging roles of cyclophilin A in regulating viral cloaking. Front Microbiol 13:828078

    Article  PubMed  PubMed Central  Google Scholar 

  • Manaswini N, Sreedevi NN, Thummala S, Saibaba KSS, Mohammed N, Satish OS (2022) Association of serum cyclophilin A levels with severity of coronary artery disease. J Lab Physicians 14:253–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masood S, Pennington ER, Simmons SO, Bromberg PA, Shaikh SR, Rice RL, Gold A, Zhang Z, Samet JM (2022) Live cell imaging of oxidative stress in human airway epithelial cells exposed to isoprene hydroxyhydroperoxide. Redox Biol 51:102281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mastrocola R, Aimaretti E, Ferreira Alves G, Cento AS, Fornelli C, Dal Bello F, Ferraris C, Goitre L, Perrelli A, Retta SF (2022) Heterozygous loss of KRIT1 in mice affects metabolic functions of the liver, promoting hepatic oxidative and glycative stress. Int J Mol Sci 23(19):11151. https://doi.org/10.3390/ijms231911151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng Y, Fan XY, Yang LJ, Xu BQ, He D, Xu Z, Wu D, Wang B, Cui HY, Wang SJ, Wang LJ, Wu XQ, Jiang JL, Xu L, Chen ZN, Li L (2020) Detachment activated CyPA/CD147 induces cancer stem cell potential in non-stem breast cancer cells. Front Cell Dev Biol 8:543856

    Article  PubMed  PubMed Central  Google Scholar 

  • Monti A, Sturlese M, Caporale A, Roger JA, Mascanzoni F, Ruvo M, Doti N (2020) Design, synthesis, structural analysis and biochemical studies of stapled AIF(370-394) analogues as ligand of CypA. Biochim Biophys Acta Gen Subj 1864:129717

    Article  CAS  PubMed  Google Scholar 

  • Opal SM, Wittebole X (2020) Biomarkers of infection and sepsis. Crit Care Clin 36:11–22

    Article  PubMed  Google Scholar 

  • Osato K, Sato Y, Ochiishi T, Osato A, Zhu C, Sato M, Swanpalmer J, Modjtahedi N, Kroemer G, Kuhn HG, Blomgren K (2010) Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation. Cell Death Dis 1:e84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pal P, Zhang P, Poddar SK, Zheng G (2022) Patent landscape of inhibitors and PROTACs of the anti-apoptotic BCL-2 family proteins. Expert Opin Ther Pat 32:1003–1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paramanantham A, Jung EJ, Go SI, Jeong BK, Jung JM, Hong SC, Kim GS, Lee WS (2021) Activated ERK signaling is one of the major hub signals related to the acquisition of radiotherapy-resistant MDA-MB-231 breast cancer cells. Int J Mol Sci 22:4940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park SH, Kim S, Lee HS, Shin I (2021) Real-time spatial and temporal analysis of the translocation of the apoptosis-inducing factor in cells. ACS Chem Biol 16:2462–2471

    Article  CAS  PubMed  Google Scholar 

  • Peng L, Jiang J, Chen HN, Zhou L, Huang Z, Qin S, Jin P, Luo M, Li B, Shi J, Xie N, Deng LW, Liou YC, Nice EC, Huang C, Wei Y (2021) Redox-sensitive cyclophilin A elicits chemoresistance through realigning cellular oxidative status in colorectal cancer. Cell Rep 37:110069

    Article  CAS  PubMed  Google Scholar 

  • Piao CS, Loane DJ, Stoica BA, Li S, Hanscom M, Cabatbat R, Blomgren K, Faden AI (2012) Combined inhibition of cell death induced by apoptosis inducing factor and caspases provides additive neuroprotection in experimental traumatic brain injury. Neurobiol Dis 46:745–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piao M, Lee SH, Kim MJ, Choi JK, Yeo CY, Lee KY (2022) Cyclophilin A promotes osteoblast differentiation by regulating Runx2. Int J Mol Sci 23:9244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Powell L, Samarakoon YH, Ismail S, Sayer JA (2021) ARL3, a small GTPase with a functionally conserved role in primary cilia and immune synapses. Small GTPases 12:167–176

    Article  CAS  PubMed  Google Scholar 

  • Qi YJ, He QY, Ma YF, Du YW, Liu GC, Li YJ, Tsao GS, Ngai SM, Chiu JF (2008) Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma. J Cell Biochem 104:1625–1635

    Article  CAS  PubMed  Google Scholar 

  • Qi ZY, Wang F, Yue YY, Guo XW, Guo RM, Li HL, Xu YY (2019) CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo. J Ovarian Res 12:118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren YX, Wang SJ, Fan JH, Sun SJ, Li X, Padhiar AA, Zhang JN (2016) CD147 stimulates hepatoma cells escaping from immune surveillance of T cells by interaction with Cyclophilin A. Biomed Pharmacother 80:289–297

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez J, Li T, Xu Y, Sun Y, Zhu C (2021) Role of apoptosis-inducing factor in perinatal hypoxic-ischemic brain injury. Neural Regen Res 16:205–213

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez J, Xie C, Li T, Sun Y, Wang Y, Xu Y, Li K, Zhang S, Zhou K, Wang Y, Mallard C, Hagberg H, Doti N, Wang X, Zhu C (2020) Inhibiting the interaction between apoptosis-inducing factor and cyclophilin A prevents brain injury in neonatal mice after hypoxia-ischemia. Neuropharmacology 171:108088

    Article  CAS  PubMed  Google Scholar 

  • Satoh K, Nigro P, Berk BC (2010) Oxidative stress and vascular smooth muscle cell growth: a mechanistic linkage by cyclophilin A. Antioxid Redox Signal 12:675–682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Satoh K, Nigro P, Matoba T, O'Dell MR, Cui Z, Shi X, Mohan A, Yan C, Abe J, Illig KA, Berk BC (2009) Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms. Nat Med 15:649–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah AM, Guo L, Morales MG, Jaichander P, Chen K, Huang H, Cano Hernandez K, Xu L, Bassel-Duby R, Olson EN, Liu N (2023) TWIST2-mediated chromatin remodeling promotes fusion-negative rhabdomyosarcoma. Sci Adv 9:eade8184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siska PJ, Decking SM, Babl N, Matos C, Bruss C, Singer K, Klitzke J, Schön M, Simeth J, Köstler J, Siegmund H, Ugele I, Paulus M, Dietl A, Kolodova K, Steines L, Freitag K, Peuker A, Schönhammer G et al (2021) Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone. J Clin Invest 131:e148225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song T, Yang M, Chen J, Huang L, Yin H, He T, Huang H, Hu X (2015) Prognosis of sepsis induced by cecal ligation and puncture in mice improved by anti-Clonorchis Sinensis cyclopholin a antibodies. Parasit Vectors 8:502

    Article  PubMed  PubMed Central  Google Scholar 

  • Su Z, Lin M, Zhang H, Li J, Wu M, Lv H, Wang J, Xie S (2020) The release of cyclophilin A from rapamycin-stimulated vascular smooth muscle cells mediated by myosin II activation: involvement of apoptosis but not autophagy. J Vasc Res 57:254–260

    Article  CAS  PubMed  Google Scholar 

  • Tamesa MS, Kuramitsu Y, Fujimoto M, Maeda N, Nagashima Y, Tanaka T, Yamamoto S, Oka M, Nakamura K (2009) Detection of autoantibodies against cyclophilin A and triosephosphate isomerase in sera from breast cancer patients by proteomic analysis. Electrophoresis 30:2168–2181

    Article  CAS  PubMed  Google Scholar 

  • Thielhelm TP, Goncalves S, Welford SM, Mellon EA, Cohen ER, Nourbakhsh A, Fernandez-Valle C, Telischi F, Ivan ME, Dinh CT (2021) Understanding the radiobiology of vestibular schwannomas to overcome radiation resistance. Cancers (Basel) 13:4575

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Luo W, Wang Y (2019) PARP-1 and its associated nucleases in DNA damage response. DNA Repair (Amst) 81:102651

    Article  CAS  PubMed  Google Scholar 

  • Williams LM, Gilmore TD (2020) Looking down on NF-κB. Mol Cell Biol 40:e00104–e00120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu Y, Ma Z, Zhang Y, Zhang M, Shi X, Zhang M, Zhang W, Liu W (2022a) The role of cyclophilins in viral infection and the immune response. J Infect 85:365–373

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Ma Z, Zhang Y, Zhang M, Zhang W, Zhang M, Shi X, Li W, Liu W (2022b) Cyclophilin A regulates the apoptosis of A549 cells by stabilizing Twist1 protein. J Cell Sci 135:jcs259018

    Article  CAS  PubMed  Google Scholar 

  • Xie Y, Li X, Ge J (2019) Cyclophilin A-FoxO1 signaling pathway in endothelial cell apoptosis. Cell Signal 61:57–65

    Article  CAS  PubMed  Google Scholar 

  • Xie Y, Li X, Ge J (2020) STAT3-CyPA signaling pathway in endothelial cell apoptosis. Cell Signal 65:109413

    Article  CAS  PubMed  Google Scholar 

  • Xin S, Liu L, Li Y, Yang J, Zuo L, Cao P, Yan Q, Li S, Yang L, Cui T, Lu J (2022) Cyclophilin A binds to AKT1 and facilitates the tumorigenicity of Epstein-Barr virus by mediating the activation of AKT/mTOR/NF-κB positive feedback loop. Virol Sin 37:913–921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xue C, Sowden M, Berk BC (2017) Extracellular cyclophilin A, especially acetylated, causes pulmonary hypertension by stimulating endothelial apoptosis, redox stress, and inflammation. Arterioscler Thromb Vasc Biol 37:1138–1146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan L, Zucker S, Toole BP (2005) Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression. Thromb Haemost 93:199–204

    Article  CAS  PubMed  Google Scholar 

  • Yin S, Wu H, Lv J, Wu X, Zhang Y, Du J, Zhang Y (2014) SHP-1 arrests mouse early embryo development through downregulation of Nanog by dephosphorylation of STAT3. PLoS One 9:e86330

    Article  PubMed  PubMed Central  Google Scholar 

  • Yuan W, Yan J, Liang Y, Jun W, Wang Z, Wang C (2013) Antiapoptotic and proapoptotic signaling of cyclophilin A in endothelial cells. Inflammation 36:567–572

    Article  CAS  Google Scholar 

  • Zhang H, Zhang SH, He HW, Zhang CX, Yu DK, Shao RG (2013) Downregulation of G3BPs inhibits the growth, migration and invasion of human lung carcinoma H1299 cells by suppressing the Src/FAK-associated signaling pathway. Cancer Gene Ther 20:622–629

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Zhu Y, Zhou Y, Fei B (2020) Interleukin 37 (IL-37) reduces high glucose-induced inflammation, oxidative stress, and apoptosis of podocytes by inhibiting the STAT3-cyclophilin A (CypA) signaling pathway. Med Sci Monit 26:e922979

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Pignolo RJ, Bram RJ (2022) Accelerated aging in cyclophilin B-deficient mice downstream of p21-Cip1/Waf1. JBMR Plus 6:e10674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou GF, Chen CX, Cai QC, Yan X, Peng NN, Li XC, Cui JH, Han YF, Zhang Q, Meng JH, Tang HM, Cai CH, Long J, Luo KJ (2022) Bracovirus sneaks into apoptotic bodies transmitting immunosuppressive signaling driven by integration-mediated eIF5A hypusination. Front Immunol 13:901593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the Natural Science Foundation of China (NO: 81871256), Natural Science Foundation of Hunan Province (NO: 2021JJ30587), and the Key Project of Health Commission of Hunan Province (NO: 202101061310).

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  1. Institute of Pathogenic Biology, Basic Medicine School, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang City, Hunan Province, 421001, People’s Republic of China

    Li Chen, Zhuo Zeng, Haodang Luo, Hua Xiao & Yanhua Zeng

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  1. Li Chen
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  2. Zhuo Zeng
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ZYH proposed the idea for the article; CL collected and analyzed literature and constructed all figures. ZYH, LHD, ZZ, and XH coordinated and jointly revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yanhua Zeng.

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Chen, L., Zeng, Z., Luo, H. et al. The effects of CypA on apoptosis: potential target for the treatment of diseases. Appl Microbiol Biotechnol 108, 28 (2024). https://doi.org/10.1007/s00253-023-12860-2

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  • DOI: https://doi.org/10.1007/s00253-023-12860-2

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