Interrelations between Apoptosis and Autophagy in Autoimmune and Malignant Diseases
Main Article Content
Abstract
The lifespan of a cell in the body oscillates between two fundamental processes, Autophagy, which ensures cell survival, even under conditions of cellular stress, and Apoptosis, which programs the end of cell life, not before the renewal of a new cell in a tissue. Overall, there is a continuation of daily life until a specified date of highlighting the length of the telomeres, in the chromosomal analysis of the cell.
Apoptosis, in the scheduling of cell life, is a normal process which is different from cell necrosis that occurs as a result of physical or chemical aggression. The decision to activate a suicide process is made based on intrinsic or extrinsic apoptotic messages. The intrinsic inducers of apotheosis come from the mitochondria or nucleus. Extrinsic inducers of apotheosis are ligands, cytokines for death receptors, (DR-Death receptors) on each cell surface.
Autophagy: is a homeostatic and catabolic processes that allows the sequestration and lysosomal degradation of cytoplasmic organs and proteins, important for maintaining genomic stability and cell survival. Autophagy is regulated by the Beclin 1 protein, which forms a complex with a class III enzyme, phospho-inoside 3-kinase (PI3K), and serves as a platform for the recruitment of other proteins critical for autophagosome formation.
Conclusions: The most important regulatory mechanism in autoimmunity and oncogenesis process are death receptors, caspases, mitochondria, the Bcl-2 family proto-oncogenes and tumor suppressor gene P53. Pharmacological manipulation of autophagy for cancer prevention and treatment will depend on our ability to successfully recognize the functional status of autophagy in tumors, and the availability of specific autophagic modulators.
Keywords:
apoptosis, autophagy, autophagy inhibitors, autophagy activators, cancer, death receptors, inflammation, inflammatory cytokine, nuclear factor-κB, P-53 Gene, Tumor Necrosis Factor
Article Details
How to Cite
UDRISTIOIU, Aurelian et al.
Interrelations between Apoptosis and Autophagy in Autoimmune and Malignant Diseases.
Medical Research Archives, [S.l.], v. 10, n. 6, june 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2886>. Date accessed: 04 dec. 2024.
doi: https://doi.org/10.18103/mra.v10i6.2886.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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[17]. Alessandri C, Barbati C, Vacirca D, et al. T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy. FASEB J. 2012;26(11):4722-4732. doi:10.1096/fj.12-206060.
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[21]. Barbati C, Stefanini L, Colasanti T, et al. Anti-D4GDI antibodies activate platelets in vitro: a possible link with thrombocytopenia in primary antiphospholipid syndrome. Arthritis Res Ther. 2019;21(1):161. Published 2019 Jul 1. doi:10.1186/s13075-019-1947-2.
[22]. Baehrecke EH. Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol. 2005 Jun;6(6):505-10. doi: 10.1038/nrm1666. PMID: 15928714.
[23]. Boone BA, Bahary N, Zureikat AH, et al. Safety and Biologic Response of Pre-operative Autophagy Inhibition in Combination with Gemcitabine in Patients with Pancreatic Adenocarcinoma. Ann Surg Oncol. 2015;22(13):4402-4410. doi:10.1245/s10434-015-4566-4.
[24]. Boya P, González-Polo RA, Casares N, et al. Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol. 2005;25(3):1025-1040. doi:10.1128/MCB.25.3.1025-1040.2005.
[25]. Bristol ML, Di X, Beckman MJ, et al. Dual functions of autophagy in the response of breast tumor cells to radiation: cytoprotective autophagy with radiation alone and cytotoxic autophagy in radiosensitization by vitamin D 3. Autophagy. 2012;8(5):739-753. doi:10.4161/auto.19313.
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[27]. Li Y, Wang LX, Pang P, et al. Tumor-derived autophagosome vaccine: mechanism of cross-presentation and therapeutic efficacy. Clin Cancer Res. 2011;17(22):7047-7057. doi: 10.1158/1078-0432.CCR-11-0951.
[28]. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999 Dec 9;402(6762):672-6. doi: 10.1038/45257. PMID: 10604474.
[29]. Lin L, Baehrecke EH. Autophagy, cell death, and cancer. Mol Cell Oncol. 2015;2(3):e985913. Published 2015 Jan 26. doi:10.4161/23723556.2014.985913.
[30]. Madeo F, Zimmermann A, Maiuri MC, Kroemer G. Essential role for autophagy in life span extension. J Clin Invest. 2015;125(1):85-93. doi:10.1172/JCI73946.
[31]. Maiuri MC, Criollo A, Tasdemir E, Vicencio JM, Tajeddine N, Hickman JA, Geneste O, Kroemer G. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L). Autophagy. 2007 Jul-Aug;3(4):374-6. doi: 10.4161/auto.4237. Epub 2007 Jul 4. PMID: 17438366.
[32]. Marinković M, Šprung M, Buljubašić M, Novak I. Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy. Oxid Med Cell Longev. 2018;2018:8023821. Published 2018 Jan 31. doi:10.1155/2018/8023821.
[33]. Miller BC, Zhao Z, Stephenson LM, Cadwell K, Pua HH, Lee HK, Mizushima NN, Iwasaki A, He YW, Swat W, Virgin HW 4th. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy. 2008 Apr;4(3):309-14. doi: 10.4161/auto.5474. Epub 2007 Dec 24. PMID: 18188005.
[34]. Wu YX, Jin SH, Cui J. Autophagy and Immune Tolerance. Adv Exp Med Biol. 2019; 1206:635-665. doi: 10.1007/978-981-15-0602-4_28. PMID: 31777005.
[35]. Nedjic J, Aichinger M, Emmerich J, Mizushima N, Klein L. Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature. 2008 Sep;455(7211):396-400. DOI: 10.1038/nature07208. PMID: 18701890.
[36]. Pan H, Chen L, Xu Y, et al. Autophagy-associated immune responses and cancer immunotherapy. Oncotarget. 2016;7(16):21235-21246. doi:10.18632/oncotarget.6908
[37]. Pua HH, Dzhagalov I, Chuck M, Mizushima N, He YW. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J Exp Med. 2007;204(1):25-31. doi:10.1084/jem.20061303.
[38]. Starr TK, Jameson SC, Hogquist KA. Positive and negative selection of T cells. Annu Rev Immunol. 2003;21:139-76. doi: 10.1146/annurev.immunol.21.120601.141107. Epub 2002 Oct 16. PMID: 12414722.
[39]. Arbogast F, Gros F. Lymphocyte Autophagy in Homeostasis, Activation, and Inflammatory Diseases [published correction appears in Front Immunol. 2018 Nov 16;9:2627]. Front Immunol. 2018;9: 1801. Published 2018 Aug 6. doi:10.3389/fimmu.2018.01801.
[40]. Takahashi Y, Meyerkord CL, Hori T, Runkle K, Fox TE, Kester M, Loughran TP, Wang HG. Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy. Autophagy. 2011 Jan;7(1):61-73. doi: 10.4161/auto.7.1.14015. Epub 2011 Jan 1. PMID: 21068542; PMCID: PMC3039731.
[41]. Eldeena SKN, El-Magd MA, Khamisa A, Ibrahim WM, Salama AF. Therapeutic implications of autophagy in cancer treatment. AJM. 2019; 2 (2):27-29. https://doi.org/10.5455/ajms.19.
[42]. Lee EJ, Kim HJ, Choi MS, Chang JE. Crosstalk between Autophagy and Inflammatory Processes in Cancer. Life (Basel). 2021;11(9):903. Published 2021 Aug 30. doi:10.3390/life11090903.