Mitochondrial depolarization

O Reilly, C.M., Fogarty, K. E., Drummond, R. M., Tuft, R. A., and Walsh, J. V., Jr., 2003, Quantitative analysis of spontaneous mitochondrial depolarizations, Biophys. J. 85, pp. 3350-3357 Okonkwo, D.O., Buki, A., Siman, R., and Povlishock, J. T., 1999, Cyclosporin A limits calcium-induced axonal damage following traumatic brain injury, Neuroreport 10, pp. 353—358 Okonkwo, D.O. and Povlishock, J. T., 1999, An intrathecal bolus of cyclosporin A before injury preserves mitochondrial integrity and attenuates axonal disruption in traumatic brain injury, J. Cereb. Blood Flow Metab. 19, pp. M3 151... 

Papucci, L., Schiavone, N., Witort, E., Donnini, M., Lapucci, A., Tempestini, A., Formigli, L., Zecchi-Orlandini, S., Orlandini, G., Carella, G., Brancato, R., and Capaccioli, S. (2003). Coenzyme QjO prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property. J. Biol. Chem. 278, 28220—28228. 

Apoptotic (caspase 3 9 activation) [antineoplastic, cytotoxic, photosensitizer] Apoptotic (DNA fragmentation, TOPII activation) (HIV-1 INT, LOX, PK) [AI, feeding stimulant] Apoptotic (per mitochondrial depolarization caspase 9 activation) (AO/FRS, COX, LOX)... 

Fig. 7.4 (a) Dose-response of the lamellarin M-induced mitochondrial depolarization in P388 cells, (b) Monitoring of the mitochondrial membrane potential (A rm) by realtime flow cytometry, using functional mitochondria isolated from P388 cells and the fluorescent probe JC-1. 

Loew, L.M., Carrington, W., Tuft, R.A., and Fay, F.S. (1994). Physiological cytosolic Ca transients evoke concurrent mitochondrial depolarizations. Proc. Natl. Acad. Sci. 97 12579-12583. 

NO, derived from L-arginine (L-Arg) by the enzyme nitric oxide synthase (NOS), is involved in the regulation of relevant physiological and pathophysiological functions. The mechanisms by which NO exerts its effects include activation of guanylate cyclase, formation of peroxynitrite, apoptosis, and COX regulation [96]. Apoptosis induction mediated by NO involves mitochondrial depolarization and is blocked by Bcl-2 overexpression [97]. 

While the role of the over activation of PARP-1 in DNA damage-induced necrotic cell death is now widely accepted, its role in apoptosis appears to hugely depend on the experimental conditions such as the cell type and nature of the stimulus. Nonetheless, Valina Dawson s group has shown that PARP activation is required for activation of the mitochondrial route of apoptosis, charaaerized by mitochondrial depolarization, release of AIF ftx>m the mitochondria to the cytosol and caspase-independent, AIF-mediated apoptosis. Notably, these findings are in line with our previous observation that PARP activation mediates mitochondrial alterations during peroxynitrite or hydrogen peroxide-induced necrotic thymocyte death. At the... 

Wang Q, Huang Y, Ni Y, Wanmg H, Hou Y. siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase 3,8,9 activation and mitochondrial depolarization. J Biomed Sci. 2007 14 783-95. 

Nieminen AL, Saylor AK, Herman B, Lemasters JJ (1994) ATP depletion rather than mitochondrial depolarization mediates hepatocyte killing after metabolic inhibition. Am J Physiol 261, C67-74. 

It was shown in primary cortical neurons that treatment with exogenous ceramide induces a signaling cascade resulting in the dephosphorylation of Akt, the pro-apoptotic protein BAD, Forkhead transcription factors, and glycogen synthase kinase-3, followed by mitochondrial depolarization, release of cytochrome c, and activation of caspase-3 (Stoica et al., 2003). If the cells were pretreated with bongkrekic acid, an antibiotic that inhibits mitochondrial... 

Outcomes of the first human clinical trials resulted from Michelakis in vitro tests from 49 patients whose freshly removed GBM were tested. These tests led researchers to conclude that "DCA. .. caused mitochondrial depolarization in GBM but not in normal brain tissue. 

Chemoimmunotherapy with cisplatin in dendritic cells pretreated with NO released by DETA-NO or isosorbide dinilrite was significantly more efficacious than cisplatin alone in mmor regression and animal survival in the B16 mouse model of melanoma. These findings demonstrated that the pretreatment of dendritic cells with NO protected the dendritic cells from cisplatin-induced apoptosis via inhibition of acid sphingomyelinase, ceramide generation, caspase-3 and 9 activation, and mitochondrial depolarization (Perrotta et al. 2(X)7). 

Chiu, S.M. and Oleinick, N.L., Dissociation of mitochondrial depolarization from cytochrome c release during apoptosis induced by photodynamic therapy, Br. J. Cancer, 84, 1099, 2001. 

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