Role of caspases

Rehm, M., Dussmann, H., Janicke, R. U., Tavare, J. M., Kogel, D. and Prehn, J. H. (2002). Single-cell fluorescence resonance energy transfer analysis demonstrates that caspase activation during apoptosis is a rapid process. Role of caspase-3. J. Biol. Chem. 277, 24506-14. 

Reproduced with permission from Zhang, J. R, Wong, C. K., and Lam, C. W. K. Role of caspases in dexamethasone-induced apoptosis and activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in human eosinophils. Clin. Exp. Immunol. 122,20-27 (2000) and Blackwell Science Ltd. 

Gupta S, Hastak K, Afaq F, Ahmad N, Mukhtar H. 2004. Essential role of caspases in epigallocatechin-3-gallate-mediated inhibition of nuclear factor kappa B and induction of apoptosis. Oncogene 23 2507-2522. 

Despite extensive research, identification of apoptotic cells remains an important unresolved issue. Apoptosis can be recognized by characteristic morphological features, which are difficult to be found in the heart. Furthermore, morphology alone does not enable recognition of cells early in the apoptotic pathway. Detection of activated caspases appears to be a reasonable way to detect apoptotic cells, given the central role of caspases in the process of apoptosis. It must be kept in mind, however, that caspases may contribute to necrotic cell death [80, 81] and caspase-independent apoptosis does occur [80]. 

Kang SJ, Wang S, Hara H, Peterson EP, Namura S, Amin-Hanjani S, et al. Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions. J Cell Biol 2000 149 613-622. 

Wang J, Lenardo MJ. Roles of caspases in apoptosis, development, and cytokine maturation revealed by homozygous gene deficiencies. J Cell Sci 2000 113 753-757. 

Cookson MR, Shaw PJ (1999) Oxidative stress and motor neurone disease. Brain Pathol 9 165-186 Cotman CW, Poon WW, Rissman RA, Blurton-Jones M (2005) The role of caspase cleavage of tau in Alzheimer disease neuropathology. J Neuropathol Exp Neurol 64 104-112 Cribbs DH, Poon WW, Rissman RA, Blurton-Jones M (2004) Caspase-mediated degeneration in Alzheimer s disease. Am J Pathol 165 353-355... 

Li M, Ona VO, Guegan C, Chen M, Jackson-Lewis V, Andrews LJ, Olszewski AJ, Stieg PE, Lee JP, Przedborski S, Friedlander RM (2000) Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science 288 335-339 Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94 491-501 Lin Y, Devin A, Cook A, Keane MM, Kelliher M, Lipkowitz S, Liu ZG (2000) The death domain kinase RIP is essential for TRAIL (Apo2L)-induced activation of IkappaB kinase and c-Jun N-terminal kinase. Mol Cell Biol 20 6638-6645... 

Benzyloxycarbonyl-Val-Ala-Asp(OMe) fluoromethyl ketone (z-VAD-FMK) is a peptide halomethyl ketone used for the inhibition of caspases and related enzymes. Because z-VAD-FMK is neutral, it passes the cell membrane and can inhibit intracellular proteolysis and is useful in understanding the role of caspases and related enzymes in cellular function. See Zhu, H., Fearnhead, H.O., and Cohen, G.M., An ICE-like protease is a common mediator of apoptosis induced by diverse stimuli in human monocytes THP.l cells, FEBS Lett. 374, 303—308, 1995 Mirzoeva, O.K., Yaqoob, P., Knox,... 

Wang J, Chai boneau R, Balasubramanian S, Sumandeep, Barke RA, Loh HH, Roy S (2001) Morphine modulates lymph node derived T lymphocyte funcdon Role of caspase-3, -8, and nitric oxide. J Leukoc Biol 70 527-536. 

Kaushal G, Ueda N, Shah S. Role of caspases (ICE/CED 3 proteases) in DNA damage and cell death in hypoxic injury. Kidney Int 1997 52 438-445. 

Edelstein C, Shi Y, Schrier R. Role of caspases in hypoxia-induced necrosis of rat renal proximaltubules. J Am Soc Nephrol 1999 10 1940-1949. 

Kaushal GP, Kaushal V, Flong X, Shah SV. Role of caspases and their regulation by Akt/protein kinase B phosphorylation pathway in cisplatin-induced injury to renal tubular epithelial cells. Kidney Int 2001 60 1726-1736. 

Choi WS, Yoon SY, Oh TH, Choi EJ, O Malley KL, Oh YJ. 1999. Two distinct mechanisms are involved in 6-hydroxydopamine- and MPP+-induced dopaminergic neuronal cell death role of caspases, ROS, and JNK. J. Neurosci. Res. 57 86-94... 

Gorman AM, Orrenius S, Ceccatelli S (1998) Apoptosis in neuronal cells role of caspases. Neuroreport 9 R49-R55... 

Monack DM, Navarre WW, Falkow S. Salmonella-induced macrophage death the role of caspase-1 in death and inflammation. Microbes Infect 2001 3 1201-12. 

Renal ischemia/ reperfusion injiuy in vivo activates caspase-1 and caspase-3 [58,67]. In a murine model of ischemia/reperfusion injury, ZVAD-fmk, a pancaspase inhibitor, was shown to attenuate reperfusion-induced DNA damage (as determined by TUNEL assay) and inflammation [67]. Recent studies by Edelstein et al. [62, 62a] help establish a link between the inflammatory aspects of the ischemic/reperfusion injury and caspase activation. In these studies it was observed that caspase 1 deficient mice were protected from ischemia-reperfusion injury. Aware that IL-18 is expressed after several cell stresses and is activated by caspase-1, the authors observed that IL-18 expression is increased in ischemia-reperfusion and caspase-1 converts IL-18 precursor to its active form. Furthermore in caspase-defi-cient mice the activity of IL-18 does not increase and the use of a neutralizing antibody to IL-18 offers protection in wild-type animals. The authors also demonstrate reduced leukocyte infiltration in caspase-1 deficient mice, completing a loop between cell injury, initiation of inflammation, and caspase-1 activation. Another study has demonstrated that caspase-3 activation during ischemia/reperfusion injury may be involved in the downregulation of calpastatin, an inhibitor of calpain [68] indicating a role of caspases for calpain activation during renal injury. 

Kronke, M. and Adam-Klages, S. Role of caspases in TNF-mediated regulation of CPLA2. FEBS Lett 531 (2002) 18-22. 

Nth-terminal kinase (JNK) and p38 MAPK activity in eosinophils is regulated by caspases. Interestingly, the caspases involved are not the common apoptosis-related caspase-3 or -8, as is the case in other cells. The elucidation of the role of caspases in eosinophil apoptosis may thus facilitate the development of more specific and effective treatments for this type of allergic inflammation [69]. 

Due to the central role of caspases in cancer, and in nem odegenerative and autoimmune disorders, they ai e subject to intense studies. A mechanistic mathematical model was formulated on the basis of newly emerging information, describing key elements of receptor-mediated and stress-induced caspase activation. Mass-conservation principles were used in conjunction witli kinetic rate laws to formulate ordinaiy differential equations that describe the temporal evolution of caspase activation. Qualitative strategies for the prevention of... 

A.G. Porter, R.U. Janicke (1999). Emerging roles of caspase-3 in apoptosis. Cell Death Dijf., 6, 99-104. 

Kumi-Diaka J, Sanderson NA, Hall A. The mediating role of caspase-3 protease in the intracellular mechanism of genistein-induced apoptosis in human prostatic carcinoma cell hnes, DU145 and LANCaP. Biol Cell 2000 92 595-604. 

Jaeschke H, Cover C, Bajt ML (2006) Role of caspases in acetaminophen-induced fiver injury. Life Sci 78(15) 1670-1676... 

Boulares AH, Ren T. Mechanism of acetaminophen-induced apoptosis In citltured Celb Roles of Caspase-3, DNA Fragmentation Factor, and the Ca2+ and N%2+ Endonuclease DNAS1L3. Pharmacol Toxicol 2004 94(l) 19-29. 

Virag L, Scott GS, Cuzzocrea S et al. Peioxynitrite-induced thymocyte apoptosis The role of caspases and poly (ADP-ribose) synthetase (PARS) activation. Immunology 1998 94(3) 345-355. 

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