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Gene Review

Casp9  -  caspase 9, apoptosis-related cysteine...

Rattus norvegicus

Synonyms: Apaf3, Casp-9-CTD, Casp9_v1, Ice-Lap6, Mch6
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Disease relevance of Casp9

  • Administration of caspase-9 inhibitor also clears the exudate that normally fills the alveoli during Pcp and decreases lung inflammation [1].
  • Furthermore, intracerebral ventricular infusion of the relatively specific caspase-9 inhibitor N-benzyloxycarbonyl-Leu-Glu-His-Asp-fluoro-methylketone before ischemia attenuated caspase-3-like activity and significantly enhanced neuronal survival in the CA1 sector [2].
  • Cloning and characterization of rat caspase-9: implications for a role in mediating caspase-3 activation and hippocampal cell death after transient cerebral ischemia [2].
  • Of significance is that the cloned promoter segments were activated by severe hypoxia, conditions inducing caspase-9 transcription [3].
  • In the presence of cytochrome c and ATP, caspase-9 and -3 were activated, which initiated chromatin condensation and DNA cleavage in rat pheochromocytoma (PC12) nuclei [4].

High impact information on Casp9


Chemical compound and disease context of Casp9


Biological context of Casp9


Anatomical context of Casp9


Associations of Casp9 with chemical compounds


Physical interactions of Casp9

  • RESULTS: Retinal detachment resulted in the time-dependent formation of the FAS-receptor/FAS-ligand complex that preceded the peak of caspase-9 activity and caspase-9/cytochrome c complex formation [21].

Regulatory relationships of Casp9

  • Finally, we show that the caspase 8 inhibitor Ac-IETD-CHO was more effective at blocking seizure-induced cell death than the caspase 9 inhibitor Ac-LEHD-CHO [22].
  • Suppressing the activation of caspase-9 inhibited the activation of caspase -3 and enhanced the cell viability and MP [18].
  • Mitochondria play an important role in the regulation of apoptosis in mammalian cells because apoptotic signals induce mitochondria to release cytochrome c. The latter interacts with Apaf-1 to activate caspase-9, which in turn activates downstream caspase-3 [16].
  • Correspondingly, expression of the mitochondrial proapoptotic factor Bax enhanced caspase 9 activation, plasma membrane blebbing, and drug-induced cytotoxicity [23].
  • Conversely, overexpression of the mitochondrial antiapoptotic factor Bcl-2 blocked caspase 9 activation, leading to an inhibition of drug-induced plasma membrane permeability and blebbing, terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity, PARP cleavage, Annexin V positivity, and drug-induced cell death [23].

Other interactions of Casp9

  • In vitro induction of apoptosis can be inhibited by the caspase-9 inhibitor (Z-LEHD-FMK) but not by the inhibitor to caspase-8 or -10 [1].
  • Apaf-1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin [24].
  • In contrast, activation of caspase-1 and caspase-9 was not observed at any of the times studied after STS exposure [25].
  • The expression of Bax, Bcl-2, caspase-3 and caspase-9 was regulated differently with aging between muscle types and in a manner not consistent with mitochondria-mediated apoptosis [26].
  • Injury-induced cytochrome c-specific cleavage of caspase-9 followed by activation of caspase-3 in mature brain correlated with marked increases in Apaf-1 and caspase-3 mRNA and protein expression [27].

Analytical, diagnostic and therapeutic context of Casp9


  1. Suppression of alveolar macrophage apoptosis prolongs survival of rats and mice with pneumocystis pneumonia. Lasbury, M.E., Durant, P.J., Ray, C.A., Tschang, D., Schwendener, R., Lee, C.H. J. Immunol. (2006) [Pubmed]
  2. Cloning and characterization of rat caspase-9: implications for a role in mediating caspase-3 activation and hippocampal cell death after transient cerebral ischemia. Cao, G., Luo, Y., Nagayama, T., Pei, W., Stetler, R.A., Graham, S.H., Chen, J. J. Cereb. Blood Flow Metab. (2002) [Pubmed]
  3. cDNA cloning and promoter analysis of rat caspase-9. Nishiyama, J., Yi, X., Venkatachalam, M.A., Dong, Z. Biochem. J. (2001) [Pubmed]
  4. Phosphorylation-dependent Akt cleavage in neural cell in vitro reconstitution of apoptosis. François, F., Grimes, M.L. J. Neurochem. (1999) [Pubmed]
  5. Molecular characterization of mitochondrial apoptosis-inducing factor. Susin, S.A., Lorenzo, H.K., Zamzami, N., Marzo, I., Snow, B.E., Brothers, G.M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., Larochette, N., Goodlett, D.R., Aebersold, R., Siderovski, D.P., Penninger, J.M., Kroemer, G. Nature (1999) [Pubmed]
  6. Caspase 9-dependent killing of hepatic stellate cells by activated Kupffer cells. Fischer, R., Cariers, A., Reinehr, R., Häussinger, D. Gastroenterology (2002) [Pubmed]
  7. Induction of apoptosis limits cytomegalovirus cross-species infection. Jurak, I., Brune, W. EMBO J. (2006) [Pubmed]
  8. GDNF-deprived sympathetic neurons die via a novel nonmitochondrial pathway. Yu, L.Y., Jokitalo, E., Sun, Y.F., Mehlen, P., Lindholm, D., Saarma, M., Arumae, U. J. Cell Biol. (2003) [Pubmed]
  9. Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels. Baydas, G., Reiter, R.J., Akbulut, M., Tuzcu, M., Tamer, S. Neuroscience (2005) [Pubmed]
  10. A tetracycline-regulated adenovirus encoding dominant-negative caspase-9 is regulated in rat brain and protects against neurotoxin-induced cell death in vitro, but not in vivo. Ebert, A.D., Chen, F., He, X., Cryns, V.L., Bohn, M.C. Exp. Neurol. (2005) [Pubmed]
  11. Taurine prevents the ischemia-induced apoptosis in cultured neonatal rat cardiomyocytes through Akt/caspase-9 pathway. Takatani, T., Takahashi, K., Uozumi, Y., Matsuda, T., Ito, T., Schaffer, S.W., Fujio, Y., Azuma, J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  12. Effect of isoflurane on neuronal apoptosis in rats subjected to focal cerebral ischemia. Kawaguchi, M., Drummond, J.C., Cole, D.J., Kelly, P.J., Spurlock, M.P., Patel, P.M. Anesth. Analg. (2004) [Pubmed]
  13. Characterization of a novel isoform of caspase-9 that inhibits apoptosis. Angelastro, J.M., Moon, N.Y., Liu, D.X., Yang, A.S., Greene, L.A., Franke, T.F. J. Biol. Chem. (2001) [Pubmed]
  14. The MUC1 oncoprotein activates the anti-apoptotic phosphoinositide 3-kinase/Akt and Bcl-xL pathways in rat 3Y1 fibroblasts. Raina, D., Kharbanda, S., Kufe, D. J. Biol. Chem. (2004) [Pubmed]
  15. Pathways of caspase-mediated apoptosis in autosomal-dominant polycystic kidney disease (ADPKD). Tao, Y., Kim, J., Stanley, M., He, Z., Faubel, S., Schrier, R.W., Edelstein, C.L. Kidney Int. (2005) [Pubmed]
  16. Polyamine depletion prevents camptothecin-induced apoptosis by inhibiting the release of cytochrome c. Yuan, Q., Ray, R.M., Johnson, L.R. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  17. Roles of insulin-like growth factor II in cardiomyoblast apoptosis and in hypertensive rat heart with abdominal aorta ligation. Lee, S.D., Chu, C.H., Huang, E.J., Lu, M.C., Liu, J.Y., Liu, C.J., Hsu, H.H., Lin, J.A., Kuo, W.W., Huang, C.Y. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  18. Mitochondrial mechanism of microvascular endothelial cells apoptosis in hyperhomocysteinemia. Tyagi, N., Ovechkin, A.V., Lominadze, D., Moshal, K.S., Tyagi, S.C. J. Cell. Biochem. (2006) [Pubmed]
  19. Tetramethylpyrazine Attenuates Adriamycin-Induced Apoptotic Injury in Rat Renal Tubular Cells NRK-52E. Cheng, C.Y., Sue, Y.M., Chen, C.H., Hou, C.C., Chan, P., Chu, Y.L., Chen, T.H., Hsu, Y.H. Planta Med. (2006) [Pubmed]
  20. Activation of caspase-9 and -3 during H2O2-induced apoptosis of PC12 cells independent of ceramide formation. Yamakawa, H., Ito, Y., Naganawa, T., Banno, Y., Nakashima, S., Yoshimura, S., Sawada, M., Nishimura, Y., Nozawa, Y., Sakai, N. Neurol. Res. (2000) [Pubmed]
  21. FAS-mediated apoptosis and its relation to intrinsic pathway activation in an experimental model of retinal detachment. Zacks, D.N., Zheng, Q.D., Han, Y., Bakhru, R., Miller, J.W. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  22. Activation of the caspase 8 pathway mediates seizure-induced cell death in cultured hippocampal neurons. Meller, R., Clayton, C., Torrey, D.J., Schindler, C.K., Lan, J.Q., Cameron, J.A., Chu, X.P., Xiong, Z.G., Simon, R.P., Henshall, D.C. Epilepsy Res. (2006) [Pubmed]
  23. Cyclophosphamide induces caspase 9-dependent apoptosis in 9L tumor cells. Schwartz, P.S., Waxman, D.J. Mol. Pharmacol. (2001) [Pubmed]
  24. Apaf-1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin. Chong, Z.Z., Kang, J.Q., Maiese, K. J. Cereb. Blood Flow Metab. (2003) [Pubmed]
  25. Effect of Ginkgo biloba (EGb 761) on staurosporine-induced neuronal death and caspase activity in cortical cultured neurons. Massieu, L., Morán, J., Christen, Y. Brain Res. (2004) [Pubmed]
  26. Sarcopenia-related apoptosis is regulated differently in fast- and slow-twitch muscles of the aging F344/N x BN rat model. Rice, K.M., Blough, E.R. Mech. Ageing Dev. (2006) [Pubmed]
  27. Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury. Yakovlev, A.G., Ota, K., Wang, G., Movsesyan, V., Bao, W.L., Yoshihara, K., Faden, A.I. J. Neurosci. (2001) [Pubmed]
  28. Caspase-9 plays a marginal role in serum starvation-induced apoptosis. Schamberger, C.J., Gerner, C., Cerni, C. Exp. Cell Res. (2005) [Pubmed]
  29. Calpeptin provides functional neuroprotection to rat retinal ganglion cells following Ca2+ influx. Das, A., Garner, D.P., Del Re, A.M., Woodward, J.J., Kumar, D.M., Agarwal, N., Banik, N.L., Ray, S.K. Brain Res. (2006) [Pubmed]
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