Tagliarino, Colleen
(Department of Radiation Oncology and Pharmacology, Case Western Reserve University)
,
Pink, John J.
(Department of Radiation Oncology and Pharmacology, Case Western Reserve University)
,
Boothman, David A.
(Department of Radiation Oncology and Pharmacology, Case Western Reserve University)
Calpains are a family of cysteine proteases existing primarily in two forms designated by the $Ca^{2+}$ concentration needed for activation in vitro, $\mu$-calpain (calpain-I) and m-calpain (calpain-II). The physiologica1 roles of calpains remain unclear. Many groups have propo...
Calpains are a family of cysteine proteases existing primarily in two forms designated by the $Ca^{2+}$ concentration needed for activation in vitro, $\mu$-calpain (calpain-I) and m-calpain (calpain-II). The physiologica1 roles of calpains remain unclear. Many groups have proposed a role for calpains In apoptosis, but their patterns of activation are not well characterized. Calpains have been implicated in neutrophil apoptosis, glucocorticoid-induced thymocyte apoptosis, as well as many other apoptotic pathways. Calpain activation in apoptosis is usually linked upstream or downstream to caspase activation, or in a parallel pathway alongside caspase activation. Calpains have been suggested to be involved in DNA fragmentation (via endonuclease activation), but also as effector proteases that cleave cellular proteins involved in DNA repair, membrane associated proteins and other homeostatic regulatory proteins. Recently, our laboratory demonstrated $\mu$-calpain activation in NAD(P)H: quinone oxidoreducatse 1 (NQO1)-expressing cells after exposure to $\beta$-lapachone, a novel quinone and potential chemo- and radio-therapeutic agent. Increased cytosolic $Ca^{2+}$ in NQO1-expressing cells after $\beta$-lapachone exposures were shown to lead to $\mu$-calpain activation. In turn, $\mu$-calpain activation was important for substrate proteolysis and DNA fragmentation associated with apoptosis. Upon activation, $\mu$-calpain translocated to the nucleus where it could proteolytically cleave PARP and p53. We provided evidence that $\beta$-lapachone-induced, $\mu$-calpain stimulated, apoptosis did not involve any of the known caspases; known apoptotic caspases were not activated after $\beta$-lapachone treatment of NQO1-expressing cells, nor did caspase inhibitors have any effect on $\beta$-1apachone-induced cell death. Elucidation of processes by which $\beta$-1apachone-stimulated $\mu$-calpain activation and calpains ability to activate endonucleases and induce apoptosis independent of caspase activity will be needed to further develop/modulate $\beta$-lapachone for treatment of human cancers that over-express NQO1.
Calpains are a family of cysteine proteases existing primarily in two forms designated by the $Ca^{2+}$ concentration needed for activation in vitro, $\mu$-calpain (calpain-I) and m-calpain (calpain-II). The physiologica1 roles of calpains remain unclear. Many groups have proposed a role for calpains In apoptosis, but their patterns of activation are not well characterized. Calpains have been implicated in neutrophil apoptosis, glucocorticoid-induced thymocyte apoptosis, as well as many other apoptotic pathways. Calpain activation in apoptosis is usually linked upstream or downstream to caspase activation, or in a parallel pathway alongside caspase activation. Calpains have been suggested to be involved in DNA fragmentation (via endonuclease activation), but also as effector proteases that cleave cellular proteins involved in DNA repair, membrane associated proteins and other homeostatic regulatory proteins. Recently, our laboratory demonstrated $\mu$-calpain activation in NAD(P)H: quinone oxidoreducatse 1 (NQO1)-expressing cells after exposure to $\beta$-lapachone, a novel quinone and potential chemo- and radio-therapeutic agent. Increased cytosolic $Ca^{2+}$ in NQO1-expressing cells after $\beta$-lapachone exposures were shown to lead to $\mu$-calpain activation. In turn, $\mu$-calpain activation was important for substrate proteolysis and DNA fragmentation associated with apoptosis. Upon activation, $\mu$-calpain translocated to the nucleus where it could proteolytically cleave PARP and p53. We provided evidence that $\beta$-lapachone-induced, $\mu$-calpain stimulated, apoptosis did not involve any of the known caspases; known apoptotic caspases were not activated after $\beta$-lapachone treatment of NQO1-expressing cells, nor did caspase inhibitors have any effect on $\beta$-1apachone-induced cell death. Elucidation of processes by which $\beta$-1apachone-stimulated $\mu$-calpain activation and calpains ability to activate endonucleases and induce apoptosis independent of caspase activity will be needed to further develop/modulate $\beta$-lapachone for treatment of human cancers that over-express NQO1.
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성능/효과
In conclusion, calpains have been implicated in a number of apoptotic and cell death pathways, however, their pattern of activation as well as their association with caspases in these pathways, remains controversial. Farther work on the ability of calpains to activate endonucleases, induce apoptosis independent of caspase activity, and their distinct role in cell death needs farther elucidation.
참고문헌 (81)
Banik NL. DeVries GH, Neuberger T, Russell T. Chakrabarti AK, and Hogan EL (1991)Calcium-activated neutral proteinase (CANP; calpain) activity in Schwann cells: immunofluorescence localization and compartmentation of mu- and mCANP. J Neurosci Res 29: 346-354
Barrett AJ, Kembhavi AA, Brown AM, Kirschke H, Knight CG, Tamai M, and Hanada K (1982) L-trans-Epoxysuccinylleucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H. and L. Biochem. J 201: 189-198
Bellamy CO, Malcomson RD, Harrison DJ, and Wyllie AH (1995) Cell death in health and disease: the biology and regulation of apoptosis. Semin Cancer Biol 6: 3-16
Buki KG, Bauer PI, and Kun E (1997) Isolation and identification of a proteinase from calf thymus that cleaves poly(ADP-ribose) polymerase and histone H1. Biochem Biophys Acta 1338: 100-106
Canu N, Dus L, Barbato C, Ciotti MT, Brancolini C, Rinaldi AM, Novak M, Cattaneo A, Bradbury A, and Calissano P (1998) Tau cleavage and dephosphorylation in cerebellar granule neurons undergoing apoptosis. J Neurosci 18: 7061-7074
Casiano CA, Martin SJ, Green DR, and Tan EM (1996) Selective cleavage of nuclear autoantigens during CD95(Fas/APO-1)-mediated T cell apoptosis. J Exp Med 184: 765-770
Chau YP, Shiah SG, Don MJ, and Kuo ML (1998) Involvement of hydrogen peroxide in topoisomerase inhibitor beta-lapachone-induced apoptosis and differentiation in human leukemia cells. Free Radic Biol Med 24: 660-670
Chua BT, Guo K, and Li P (2000) Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases. J Biol Chem 275: 5131-5135
Cottin P, Vidalenc PL, and Ducastaing A (1981) $Ca^{2+}$ -dependent association between a $Ca^{2+}$ -activated neutral proteinase(CaANP) and its specific inhibitor. FEBS Lett 136: 221-224
Croall DE, Morrow JS, and Demartino GN (1986) Limited proteolysis of the erythrocyte membrane skeleton by calcium-dependent proteinases. Biochim Biophys Acta 882: 287-296
Drenou B, Blancheteau V, Burgess DH, Fauchet R, Charron DJ, and Mooney NA (1999) A caspase-independent pathway of MHC class II antigen-mediated apoptosis of human B lymphocytes. J. Immunol 163: 4115-4124
Eby MT, Jasmin A, Kumar A, Sharma K, and Chaudhary PM (2000) TAJ, a novel member of the tumor necrosis factor receptor family, activates the c-Jun N-terminal kinase pathway and mediates caspase-independent cell death. J Biol Chem 275: 15336-15342
Goll DE, Thompson VF, Taylor RG, and Zalewska T (1992). Is calpain activity regulated by membranes and autolysis or by calcium and calpastatin? Bioessays 14: 549-556
Janicke RU, Ng P, Sprengart ML, and Porter AG (1998) Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis. J. Biol Chem 273: 15540-15545
Janicke RU, Walker PA, Lin XY, and Porter AG (1996) Specific cleavage of the retinoblastoma protein by an ICE-like protease in apoptosis. EMBO J 15: 6969-6978
Kapprell HP and Goll DE (1989) Effect of $Ca^{2+}$ on binding of the calpains to calpastatin. J Biol Chem 264: 17888-17896
Kato M, Nonaka T, Maki M, Kikuchi H, and Imajoh-Ohmi S (2000) Caspases cleave the amino-terminal calpain inhibitory unit of calpastatin during apoptosis in human jurkat T cells. J Biochem 127: 297-305
Kaufmann SH (1989) Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note. Cancer Res 49: 5870-5878
Kawasaki H, Emori Y, Imajoh-Ohmi S, Minami Y, and Suzuki K (1989) Identification and characterization of inhibitory sequences in four repeating domains of the endogenous inhibitor for calcium-dependent protease. J Biochem 106: 274-281
Kawasaki H and Kawashima S (1996) Regulation of the calpain-calpastatin system by membranes. Mol Membr Biol 13: 217-224
Kerr JF, Wylllie AH, and Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239-257
Langenfeld J, Kiyokawa H, Sekula D, Boyle J, and Dmitrovsky E (1997) Posttranslational regulation of cyclin D1 by retinoic acid: a chemoprevention mechanism. Proc Natl Acad Sci USA 94: 12070-12074
Lankiewicz S, Marc Luetjens C, Truc Bui N, Krohn AJ, Poppe M, Cole GM, Saido TC, and Prehn JH (2000) Activation of calpain I converts excitotoxic neuron death into a caspase independent cell death. J Biol Chem 275: 17064-17071
Lazebnik YA, Kaufmann SH, Desnoyer S, Poirier GG, and Earnshaw WC (1994) Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE Nature 371: 346-347
Li CJ, Li YZ, Pinto AV, and Pardee AB (1999) Potent inhibition of tumor survival in vivo by beta-lapachone plus taxol:combining drugs imposes different artificial checkpoints. Proc Natl Acad Sci USA 96: 13369-13374
Maki M, Takano E, Osawa T, Ooi T, Murachi T, and Hatanaka M (1988) Analysis of structure-function relationship of pig calpastatin by expression of mutated cDNAs in Escherichia coli. J Biol Chem 263: 10254-10261
Marin A, Lopez de Cerain A, Hamilton E, Lewis AD, Martinez Penuela JM, Idoate MA, and Bello J (1997) DT-diaphorase and cytochrome B5 reductase in human lung and breast tumours. Br J Cancer 76: 923-929
McGinnis KM, Gnegy ME, Park YH, Mukerjee N, and Wang KK (1999) Procaspase-3 and poly(ADP)ribose polymerase(PARP) are calpain substrates. Biochem Biophys Res Commun 263: 94-99
McGinnis KM, Whitton MM, Gnegy ME, and Wang KK (1998) Calcium/calmodulin-dependent protein kinase IV is cleaved by cells undergoing apoptosis. J Biol Chem 273: 19993-20000
Nakagawa T and Yuan J (2000) Cross-talk between two cysteine protease families: activation of caspase-12 by calpain in apoptosis. J Cell Biol 150: 887-894
Nath R, Raser KJ, McGinnis K, Nadimpalli R, Stafford D, and Wang KK (1996a) Effects of ICE-like protease and calpain inhibitors on neuronal apoptosis. Neuroreport 8: 249-255
Nath R, Raser KJ, Stafford D, Hajimohammadreza I, Posner A, Allen H, Talanian RV, Yuen P, Gilbertsen RB, and Wang KK (1996b) Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptrotic cells: contributory roles of both protease families in neuronal apoptosis. Biochem J 319: 683-690
Nicholson DW (1999) Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ 6: 1028-1042
Nixon RA, Saito KI, Grynspan F, Griffin WR, Katayama S, Honda T, Mohan PS, Shea TB, and Beermann M (1994) Calcium-activated neutral proteinase (calpain) system in aging and Alzheimer's disease. Ann N Y Acad Sci 747: 77-91
Okuno S, Shimizu S, Ito T, Nomura M, Hamada E, Tsujimoto Y, and Matsuda H (1998) Bcl02 prevents caspase-independent cell death. J Biol Chem 273: 34272-34277
Pariat M, Carillo S, Molinari M, Salvat C, Debussche L, Bracco L, Milner J, and Piechaczyk M (1997) Proteolysis by calpains: a possible contribution to degradation of p53. Mol Cell Biol 17: 2806-2815
Patel T, Gores GJ, and Kaufmann SH (1996) The role of proteases during apoptosis. FASEB J 10: 587-597
Pink JJ, Planchon SM, Tagliarino C, Varnes ME, Siegel D, and Boothman DA (2000a) NAD(P)H:Quinone oxidoreductase activity is the principal determinant of beta-lapachone cytotoxicity. J Biol Chem 275: 5416-5424
Pink JJ, Wuerzberger-Davis S, Tagliarino C, Planchon SM, Yang X, Froelich CJ, and Boothman DA (2000b) Activation of a cysteine protease in MCF-7 and T47D breast cancer cells during beta-lapachone-mediated apoptosis. Exp Cell Res 255: 144-155
Planchon SM, Pink JJ, Tagliarino C, Bornmann WG, Varnes ME, and Boothman DA (2001) Beta-lapachone-induced apoptosis in human prostate cancer cells: involvement of nqo1/xip3. Exp Cell Res 267: 95-106
Planchon SM, Wuerzberger S, Frydman B, Witiak DT, Hutson P, Church DR, Wilding G, and Boothman DA (1995) Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: a p53-independent response. Cancer Res 55: 3706-3711
Planchon SM, Wuerzberger-Davis SM, Pink JJ, Robertson KA, Bornmann WG, and Boothman DA (1999) Bcl-2 protects against beta-lapachone-mediated caspase 3 activation and apoptosis in human myeloid leukemia (HL-60) cells. Oncol Rep 6: 485-492
Rami A, Agarwal R, Botez G, and Winckler J (2000) mu-Calpain activation, DNA fragmentation, and synergistic effects of caspase and calpain inhibitors in protecting hippocampal neurons from ischemic damage. Brain Res 866: 299-312
Richard I, Roudaut C, Saenz A, Pogue R, Grimbergen JE, Anderson LV, Beley C, Cobo Am, de Diego C, Eymard B, Gallano P, Ginjaar HB, Lasa A, Pollitt C, Topaloglu H, Urtizberea JA, de Visser M, van der Kooi A, Bushby K, Bakker E, Lopez de Munain A, Fardeau M, and Beckmann JS (1999) Calpainopathy-a survey of mutations and polymorphisms. Am J Hum Genet 64: 1524-1540
Roberts-Lewis JM, Marcy VR, Zhao Y, Vaught JL, Siman R, Lewis ME (1993) Aurintricarboxylic acid protects hippocampal neurons from NMDA- and ischemia-induced toxicity in vivo. J Neurochem 61: 378-381
Ruiz-Vela A, Gonzalez de Buitrago G, Martinez AC (1999) Implication of calpain in caspase activation during B cell clonal deletion. EMBO J 18: 4988-4998
Sakai K, Akanuma H, Imahori K, and Kawashima S (1987) A unique specificity of a calcium activated neutral protease indicated in histone hydrolysis. J Biochem 101: 911-918
Schoenwaelder SM and Burridge K (1999). Evidence for a calpeptin-sensitive protein-tyrosine phosphatase upstream of the small GTPase Rho. A novel role for the calpain inhibitor calpeptin in the inhibition of protein-tyrosine phosphatases. J Biol Chem 274: 14359-14367
Shiah SG, Chuang SE, Chau YP, Shen SC, and Kuo ML (1999) Activation of c-Jun NH2-terminal Kinase and subsequent CPP32/Yama during topoisomerase inhibitor beta-lapachone-induced apoptosis through an oxidation-dependent pathway. Cancer Res 59: 391-398
Stennicke HR, Jurgensmeier JM, Shin H, DEveraux Q, Wolf BB, Yang X, Zhou Q, Ellerby HM, Ellerby LM, Bredesen D, Green DR, Reed JC, Froelich CJ, and Salvesen GS (1998) Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem 273: 27084-27090
Stepczynska A, Lauber K, Engels IH, Janssen O, Kabelitz D, Wesselborg S, and Schulze-Osthoff K (2001) Staurosporine and conventional anticancer drugs induce overlapping, yet distinct pathways of apoptosis and caspase activation. Oncogene 20: 1193-1202
Tenev T, Marani M, McNeish I, and Lemoine NR (2001) Procaspase-3 overexpression sensitises ovarian cancer cells to proteasome inhibitors. Cell Death Differ 8: 256-264
Villa PG, Henzel WJ, Sensenbrenner M, Henderson CE, and Pettmann B (1998) Calpain inhibitors, but not caspase inhibitors, prevent actin proteolysis and DNA fragmentation during apoptosis. J Cell Sci 111: 713-722
Wang KK, Posmantur R, Nadimpalli R, Nath R, Mohan P, Nixon RA, Talanian RV, Keegan M, Herzog L, and Allen H (1998) Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis. Arch Biochem Biophys 356: 189-196
Wolf BB, Goldstein JC, Stennicke HR, Beere H, Amarante Mendes GP, Salvesen GS, and Green DR (1999) Calpain functions in a caspase-Independent manner to promote apoptosis-like events during platelet activation. Blood 94: 1683-1692
Wood DE, Thomas A, Devi LA, Berman Y, Beavis RC, Reed JC, and Newcomb EW (1998) Bax cleavage is mediated by calpain during drug-induced apoptosis. Oncogene 17: 1069-1078
Wuerzberger SM, Pink JJ, Planchon SM, Byers KL, Bornmann WG, Boothman DA (1998) Induction of apoptosis in MCF-7:WS8 breast cancer cells by beta-lapachone. Cancer Res 58: 1876-1885
Yoshimura N, Hatanaka M, Kitahara A, Kawaguchi N, and Murachi T (1984). Intracellular localization of two distinct $Ca^{2+}$ -proteases (calpain I and calpain II) as demonstrated by using discriminative antibodies. J Biol Chem 259: 9847-9452
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