¿Aún no está registrado?

Cree su cuenta. Regístrese en Elsevier y obtendrá: información relevante, máxima actualización y promociones exclusivas.

Registrarme ahora
Solicitud de permisos - Ayuda - - Regístrese - Teléfono 902 888 740
Buscar en

Indexada en:

Index Medicus/MEDLINE, Excerpta Medica/EMBASE, SCOPUS, Science Citation Index Expanded, Journal Citation Reports/Science Edition, IBECS


  • Factor de Impacto: 1,106 (2016)
  • SCImago Journal Rank (SJR):0,314
  • Source Normalized Impact per Paper (SNIP):0,383

© Thomson Reuters, Journal Citation Reports, 2016

Endocrinol Nutr 2001;48:272-80 - DOI: 10.1016/S1575-0922(01)74406-3
Fundamentos de la apoptosis celular: interés en endocrinología
The basics of cellular apoptosis: interest in endocrinology
L.M. Frago, A. Arroba, J.A. Chowen,
Unidad de Investigación. Hospital Niño Jesús. Madrid.

El número de células de un organismo está regulado por un balance entre la proliferación, la diferenciación y la muerte celular. Sin embargo, el equilibrio entre la proliferación y la muerte de una población celular puede estar alterado por un aumento o una disminución de uno de estos procesos. En particular, cuando la muerte celular ocurre en menor medida de lo normal, se observan alteraciones que conllevan acumulación de células. De igual forma, un aumento de la muerte celular podría ser responsable de la pérdida de células y sus enfermedades asociadas. A este respecto, la muerte celular se ha considerado como un mecanismo relevante que contribuye a la regulación de la vida.


The number of cells in an organism is determined by a balance between cell proliferation, differentiation and death. However, the normal equilibrium between proliferation and death of a specific cell population is sometimes altered by an increase or decrease in either of these processes. For example, when cell death occurs to a lesser extent than required the result is an abnormal accumulation of cells. Likewise, an increase in cell death results in the loss of cells and possibly an associated disease. In this respect, cell death is considered to be an important mechanism for the regulation of life.

Palabras Clave
Apoptosis, Caspasas, Hormonas, Glándulas, Hipófisis, Diabetes
Key words
Apoptosis, Caspases, Hormones, Pituitary, Diabetes
El Texto completo solo está disponible en PDF
A.H. Wyllie,J.F. Kerr,A.R. Currie
Cell death: the significance of apoptosis
Int Rev Cytol, 68 (1980), pp. 251-307
R.A. Lockshin,C.M. Williams
Programmed cell death: cytology of degeneration in the intersegmental muscles of silkmoth
J Insect Physiol, 11 (1965), pp. 123-133
L.M. Schwartz,S. Smith,M.E.E. Jones,B.A. Osborne
Do all programmed cell death occur via apoptosis?
Proc Natl Acad Sci USA, 90 (1993), pp. 980-984
M.D. Jacobson,M. Weil,M.C. Raff
Programmed cell death in animal development
Cell, 88 (1997), pp. 347-354
C.B. Thompson
Apoptosis in the pathogenesis and treatment of disease
Science, 267 (1995), pp. 1456-1462
C. Borner,L. Monney
Apoptosis without caspases: an inefficient molecular guillotine?
Cell Death Differ, 6 (1999), pp. 497-507 http://dx.doi.org/10.1038/sj.cdd.4400525
S. Sen,M. D'Incalci
Apoptosis: biochemical events and relevance to cancer chemotheraphy
FEBS Lett, 307 (1992), pp. 122-127
Z. Darzynkiewicz,G. Juan,X. Li,W. Gorczyca,M.A. Hotz,P. Lassota
Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death (necrosis)
Cytometry, 27 (1997), pp. 1-20
I. Scovassi,G.G. Poirier
Poly(ADP-ribosylation) and apoptosis
Mol Cell Biochem, 199 (1999), pp. 125-137
Y. Gavrieli,Y. Sherman,S.A. Ben-Sasson
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation
J Cell Biol, 119 (1992), pp. 493-501
G.M. Cohen
ICE-like proteases (caspases): the executioners of apoptosis
Biochemical J, 326 (1997), pp. 1-16
G. Núñez,M.A. Benedict,Y. Hu,N. Inohara
Caspases: the proteases of the apoptotic pathway
Oncogene, 17 (1998), pp. 3237-3245 http://dx.doi.org/10.1038/sj.onc.1202581
G.Y. Salvesen,V.M. Dixit
Caspase activation: the induced-proximity model
Proc Natl Acad Sci USA, 96 (1999), pp. 10964-10967
Q. Zhou,G.S. Salvesen
Activation of pro-caspase-9 by serine proteases includes a non-canonical specifity
Biochem J, 324 (1997), pp. 361-364
E.A. Slee,M.T. Harte,R.M. Kluck,B.B. Wolf,C.A. Casiano,D.D. Newmeyer
Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases –2, –3, –6, –7, –8 and –10 in a caspase –9– dependent manner
J Cell Biol, 144 (1999), pp. 281-292
D.W. Nicholson,N.A. Thornberry
Caspases: killer proteases
Trends Biochem, 22 (1997), pp. 199-306
M. Muzio,B.R. Stockwell,H.R. Stennicke,G.S. Salvesen,V.M. Dixit
An induced proximity model for caspase-8 activation
J Biol Chem, 273 (1998), pp. 2926-2930
J.J. Chou,H. Matsuo,H. Duan,G. Wagner
Solution structure of the RIADD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment
Cell, 94 (1998), pp. 171-180
H.R. Stennicke,J.M. Jurgensmeier,H. Shin,Q. Deveraux,B.B. Wolf,X. Yang
Pro-caspase-3 is a major physiologic target of caspase-8
J Biol Chem, 273 (1998), pp. 27084-27090
H. Zou,W.J. Henzel,X. Liu,A. Lutschg,X. Wang
Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3
Cell, 90 (1997), pp. 405-413
S.M. Srinivasula,M. Ahmad,T. Fernandes-Alnemri,E.S. Alnemri
Autoactivation of procaspase-9 by Apaf-1 mediated oligomerization
Mol Cell, 1 (1998), pp. 949-957
P. Li,D. Nijhawan,I. Budihardjo,S.M. Srinivasula,M. Ahmad,E.S. Alnemri
Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade
Cell, 91 (1997), pp. 479-489
G. Kroemer,B. Dellaporta,M. Resch-Rigon
The mitochondrial death/life regulator in apoptosis and necrosis
Annu Rev Physiol, 60 (1998), pp. 619-642 http://dx.doi.org/10.1146/annurev.physiol.60.1.619
D.R. Green,J.C. Reed
Mitochondria and apoptosis
Science, 281 (1998), pp. 1309-1312
X. Liu,C.N. Kim,J. Yang,R. Jemmerson,X. Wang
Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c
Cell, 86 (1996), pp. 147-157
R.M. Kluck,E. Bossy-Wetzel,D.R. Green,D.D. Newmeyer
The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis
Science, 275 (1997), pp. 1132-1136
K. Kuida,T.F. Haydar,C.Y. Kuan,Y. Gu,C. Taya,H. Karasuyama
Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase-9
Cell, 94 (1998), pp. 325-327
H. Yoshida,Y-Y Kong,R. Yoshida,A.J. Elia,A. Hakem,R. Hakem
Apaf-1 is required for mitochondrial pathways of apoptosis and brain development
Cell, 94 (1998), pp. 739-750
M.O. Hengartner
Death cycle and swiss army knives
Nature, 391 (1998), pp. 441-442 http://dx.doi.org/10.1038/35036
Q.L. Deveraux,R. Takahashi,G.H. Salvesen,J.C. Reed
X-linked IAP is a direct inhibitor of cell-death proteases
Nature, 388 (1997), pp. 300-304 http://dx.doi.org/10.1038/40901
A.G. Uren,M. Pakusch,C.J. Hawkins,K.L. Puls,D.L. Vauls
Clonning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors
Proc Natl Acad Sci USA, 93 (1996), pp. 4974-4978
J. Yang,X. Liu,K. Bhalla,C.N. Kim,A.M. Ibrado,J. Cai
Prevention of apoptosis by Bcl-2: release os cychrome c from mitochondria blocked
Science, 275 (1997), pp. 1132-1136
G. Pan,K. O'Rourke,V.M. Dixit
Caspase-9, Bcl-Xl, and Apaf-1 form a ternary complex
J Biol Chem, 273 (1998), pp. 5841-5845
Y. Hu,M.A. Benedict,D. Wu,N. Inohara,G. Núñez
Bcl-Xl interacts with Apaf-1 and inhibits Apaf-1 dependent caspase-9 activation
Proc Natl Acad Sci USA, 95 (1998), pp. 4386-4391
M.P. Boldin,T.M. Goncharov,Y.V. Goltsev,D. Wallach
Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1 and TNF receptor-induced cell death
Cell, 85 (1996), pp. 803-815
H. Li,H. Zhu,C. Xu,J. Yuan
Cleavage of BID by caspase-8 mediates the mitochondrial damage in the Fas pathway of apoptosis
Cell, 94 (1998), pp. 491-501
S. Desagher,A. Osen-Sand,A. Nichols,R. Eskes,S. Montessuit,S. Laupeer
Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis
J Cell Biol, 144 (1999), pp. 891-901
C. Stroh,K. Schulze-Osthoff
Death by a thousand cuts: an ever increasing list of caspase substrates
Cell Death Differ, 5 (1998), pp. 997-1000 http://dx.doi.org/10.1038/sj.cdd.4400451
M. Van de Craen,W. Declercq,I. Van den brande,W. Fiers,P. Vandenabeele
The proteolytic procaspase activation network: an in vitro analysis
Cell Death Differ, 6 (1999), pp. 1117-1124 http://dx.doi.org/10.1038/sj.cdd.4400589
E.H. Cheng,D.G. Kirsch,R.J. Clem,R. Ravi,M.B. Kastan,A. Bedi
Conversion of Bcl-2 to a Bax-like death effector by caspases
Science, 278 (1997), pp. 1966-1968
C. Scaffidi,S. Fulda,A. Srinivasan,C. Friesen,F. Li,K.J. Tomaselli
Two CD95 (APO-1/Fas) signaling pathway
EMBO J, 17 (1998), pp. 1675-1687 http://dx.doi.org/10.1093/emboj/17.6.1675
Y. Jiang,J.D. Woronicz,W. Liu,D.V. Goeddel
Prevention of constitutive TNF receptor 1 signaling by silencer of death domains
Science, 283 (1999), pp. 543-546
D. De Valck,D.Y. Jin,K. Heyninck,M. Van de Craen,R. Contreras,W. Fiers
The zinc finger protein A20 interacts with a novel antiapoptotic protein which is cleaved by specific caspases
Oncogene, 18 (1999), pp. 4182-4190 http://dx.doi.org/10.1038/sj.onc.1202787
C. Wang,M.W. Mayo,R.G. Korneluk,D.V. Goeddel,A.S. Baldwin Jr.
NFkappa B antiapoptotis: induction of TRAF1 annd TRAF2 and c-IAP 1 and c-IAP 2 to supress caspase-8 activation
Science, 281 (1998), pp. 1680-1683
D. Vercammen,P. Vandenabeele,R. Beyaert,W. Declercq,W. Fiers
Tumour necrosis factor-induced necrosis versus anti-Fas-induced apoptosis in L929 cells
Cytokine, 9 (1997), pp. 801-808 http://dx.doi.org/10.1006/cyto.1997.0252
W. Kiess,B. Gallaher
Hormonal control of programmed cell death/apoptosis
Eur J Endocrinol, 138 (1998), pp. 482-491
B.S. McEwen,P.G. Davis,B. Parsons,D.W. Pfaff
The brain as a target for steroid hormone action
Annu Rev Neurosci, 2 (1979), pp. 65-112 http://dx.doi.org/10.1146/annurev.ne.02.030179.000433
E. Ahlbom,L. Grandison,B. Zhivotovsky,S. Ceccatelli
Termination of lactation induces apoptosis and alters the expression of the Bcl-2 family members in the rat anterior pituitary
Endocrinology, 139 (1998), pp. 2465-2471 http://dx.doi.org/10.1210/endo.139.5.5985
L.G. Goluboff,C. Ezrin
Effect of pregnancy on the somatotrophs and the prolactin cell of the human adenohypophysis
J Clin Endocrinol Metab, 29 (1969), pp. 1533-1538 http://dx.doi.org/10.1210/jcem-29-12-1533
L.M. García-Segura,P. Cardona-Gómez,F. Naftolin,J.A. Chowen
Estradiol upregulates Bcl-2 expression in adult brain neurons
Neuroendocrinology, 9 (1998), pp. 593-597
L.M. García-Segura,G.P. Cardona-Gómez,J.A. Chowen,I. Azcoitia
Insulin-like growth factor-I receptor and estrogen receptors interact in the promotion of neuronal survival and neuroprotection
J Neurocytol, 29 (2000), pp. 425-437
H.L. Cheng,E.L. Feldman
Bidirectional regulation of p38 kinase and c-Jun N-terminal protein kinase by Insulin-like growth factor-I
J Biol Chem, 273 (1998), pp. 14560-14565
N. Cheng,L. Dong,M. Schachner
Prevention of neuronal cell death by neural adhesion molecules L1 and CHL1
J Neurobiol, 38 (1999), pp. 428-439
T. Chittenden,E.A. Harrington,R. O'Connor,C. Flemington,R.J. Lutz,G.I. Evan
Induction of apoptosis by the Bcl-2 homologue Bak
Nature, 374 (1995), pp. 733-736 http://dx.doi.org/10.1038/374733a0
C.G. Print,K.L. Loveland
Germ cell suicide: new insights into apoptosis during spermatogenesis
K. Boekelheide,S.L. Fleming,K.J. Johnson,S.R. Patel,H.A. Schoenfeld
Role of Sertoli cells in injury-associated testicular germ cell apoptosis
Proc Soc Exp Biol Med, 225 (2000), pp. 105-115
G. Dirami,N. Ravindranath,H.K. Kleinman,M. Dym
Evidence that basement membrane prevents apoptosis of Sertoli cells in vitro in the absence of known regulators of sertoli cell function
Endocrinology, 136 (1995), pp. 4439-4447 http://dx.doi.org/10.1210/endo.136.10.7664664
F. Sinowatz,W. Amselgruber,J. Plendl,S. Kolle,C. Neumuller,G. Boos
Effects of hormones on the prostate in adult and aging men and animals
Microsc Res Tech, 30 (1995), pp. 282-292 http://dx.doi.org/10.1002/jemt.1070300404
A. Amsterdam,A. Dantes,N. Selvaraj,D. Aharoni
Apoptosis in steroidogenic cells: structure-function analysis
Steroids, 62 (1997), pp. 207-211
K. Reynaud,M.A. Driancourt
Oocyte attrition
Mol Cell Endocrinol, 163 (2000), pp. 1001-1108
S.D. Westfall,I.R. Hendry,K.L. Obholz,B.R. Rueda,J.S. Davis
Putative role of the phosphatidylinositol 3-kinase-Akt signaling pathway in the survival of granulosa cells
Endocrine, 12 (2000), pp. 315-321 http://dx.doi.org/10.1385/ENDO:12:3:315
Apoptosis II: the molecular basis of apoptosis in disease. Current Comminications in Cell and Molecular Biology 8,
C.S. Atwood,M. Ikeda,B.K. Vonderhaar
Involution of mouse mammary glands in whole organ culture: a model for studying programmed cell death
Biochem Biophys Res Commun, 207 (1995), pp. 860-867 http://dx.doi.org/10.1006/bbrc.1995.1265
O.D. Slayden,J.J. Hirst,R.M. Brenner
Estrogen action in the reproductive tract of rhesus monkeys during antiprogestin treatment
Endocrinology, 132 (1993), pp. 1845-1856 http://dx.doi.org/10.1210/endo.132.4.8462480
K.C. Akcali,S.A. Khan,B.C. Moulton
Effect of decidualization on the expresion of bax and bcl-2 in the rat uterine endometrium
Endocrinology, 137 (1996), pp. 3123-3131 http://dx.doi.org/10.1210/endo.137.7.8770938
H. Zulewski,E.J. Abraham,M.J. Gerlach,P.B. Daniel,W. Moritz,B. Muller
Multipotencial nestin-positive stem cells isolated from adult pancreatic islet differenciate ex vivo into pancreatic endocrine, exocrine and hepatic phenotypes
Diabetes, 50 (2001), pp. 521-533
T. Mandrup-Poulsen
b-Cell Apoptosis
Diabetes, 50 (2001), pp. S58-S63
A. Ammendrup,A. Maillard,K. Nielsen,N. Aabenhus Andersen,P. Serup,O. Dragsbaek Madsen
The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells
Diabetes, 49 (2000), pp. 1468-1476
T. Gurlo,K. Kawamura,H. Von Grafenstein
Role of inflammatory infiltrate in activation and effector function of cloned islet reactive nonobese diabetic CD8+ T cells. Involvement of a nitric oxide-dependent pathway
J Immunol, 163 (1999), pp. 5770-5780
T. Mandrup-Poulsen
The role of interleukin-1 in the pathogenesis of IDDM
Diabetologia, 39 (1996), pp. 1005-1029
C. Cailleau,A. Diu-Hercend,E. Ruuth,R. Westwood,C. Carnaud
Treatment with neutralizing antibodies specific for IL-1 beta prevents cyclophosphamide-induced diabetes in nonobese diabetic mice
Diabetes, 46 (1997), pp. 937-940
M. Federici,M. Hribal,L. Perego,M. Ranalli,Z. Caradonna,C. Perego
High glucose Causes apoptosis in cultured human pancreas islets of Langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program
Diabetes, 50 (2001), pp. 1290-1301
M. Shimabukuro,M.Y. Wang,Y.T. Zhou,C.B. Newgard,R.H. Unger
Protection against lipoapoptosis of beta cells through leptin-dependent manteinance of Bcl-2 expression
pp. 9558-9561
I.B. Efanova,S.V. Zaitsev,B. Zhivotovsky,M. Kohler,S. Efendic,S. Orrenius
Glucose and tolbutamida induce apoptosis in pancreatic betacells: a process dependent on intracellular Ca2+ concentration
J Biol Chem, 273 (1998), pp. 33501-33507
E.L. Saafi,B. Konarkowska,S. Zhang,J. Kistler,G.J. Cooper
Ultrastructural evidence that apoptosis is the mechanism by which human amylin evokes death in RINm5F pancreatic islet beta-cells
Cell Biol Int, 25 (2001), pp. 339-350 http://dx.doi.org/10.1006/cbir.2000.0643
M. Andrikoula,A. Tsatsoulis
The role of Fas-mediated apoptosis in thyroid disease
Eur J Endocrinol, 144 (2001), pp. 561-568
N. Mitsiades,V. Poulaki,G. Mastorakos,S. Tselenis-Balafouta,V. Kotoula,D.A. Koutras
Fas ligand expression in thyroid carcinomas: a potential mechanism of inmune evasion
J Clin Endocrinol Metab, 84 (1999), pp. 2924-2932 http://dx.doi.org/10.1210/jcem.84.8.5917
J. Feldkamp,E. Pascher,A. Perniok,V.A. Scherbaum
Fas-mediated apoptosis is inhibited by TSH and iodine in moderate concentrations in primary human thyrocytes in vitro
Horm Metab Res, 31 (1999), pp. 355-358 http://dx.doi.org/10.1055/s-2007-978753
Correspondencia. Dra. J.A. Chowen. Unidad de Investigación. Hospital Niño Jesús. Avda. Menéndez Pelayo, 65. 28009 Madrid. (J.A. Chowen endocrino@hnjs.insalud.es)
Copyright © 2001. Sociedad Española de Endocrinología y Nutrición