Rescue from death but not from functional impairment: caspase inhibition protects dopaminergic cells against 6-hydroxydopamine-induced apoptosis but not against the loss of their terminals

Iron may play an important role in Parkinson's disease (PD) since it can induce oxidative stress-dependent neurodegeneration. The objective of this study was to determine whether the iron chelator, phytic acid (IP6) can protect against 6-hydroxydopamine- (6-OHDA-) induced apoptosis in immortalized rat mesencephalic dopaminergic cells under normal and iron-excess conditions. Caspase-3 activity was increased about 6-fold after 6-OHDA treatment (compared to control; ) and 30 μmol/L IP6 pretreatment decreased it by 38% (). Similarly, a 63% protection () against 6-OHDA induced DNA fragmentation was observed with IP6 pretreatment. Under iron-excess condition, a 6-fold increase in caspase-3 activity () and a 42% increase in DNA fragmentation () with 6-OHDA treatment were decreased by 41% () and 27% (), respectively, with 30 μmol/L IP6. Together, our data suggest that IP6 protects against 6-OHDA-induced cell apoptosis in both normal and iron-excess conditions, and IP6 may offer neuroprotection in PD.

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Critical role of ASK1 in the 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2006.03730.x ◽

2006 ◽

Vol 97 (1) ◽

pp. 234-244 ◽

Cited By ~ 83

Author(s):

Mingxing Ouyang ◽

Xun Shen

Keyword(s):

Critical Role ◽

Human Neuroblastoma ◽

Induced Apoptosis ◽

6 Hydroxydopamine

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Resveratrol delays 6-hydroxydopamine-induced apoptosis by activating the PI3K/Akt signaling pathway

Experimental Gerontology ◽

10.1016/j.exger.2019.110653 ◽

2019 ◽

Vol 124 ◽

pp. 110653 ◽

Cited By ~ 6

Author(s):

Nanqu Huang ◽

Ying Zhang ◽

Mingji Chen ◽

Hai Jin ◽

Jing Nie ◽

...

Keyword(s):

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Induced Apoptosis ◽

6 Hydroxydopamine

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IAP Suppression of Apoptosis Involves Distinct Mechanisms: the TAK1/JNK1 Signaling Cascade and Caspase Inhibition

Molecular and Cellular Biology ◽

10.1128/mcb.22.6.1754-1766.2002 ◽

2002 ◽

Vol 22 (6) ◽

pp. 1754-1766 ◽

Cited By ~ 146

Author(s):

M. Germana Sanna ◽

Jean da Silva Correia ◽

Odile Ducrey ◽

Jongdae Lee ◽

Ken Nomoto ◽

...

Keyword(s):

Signaling Cascade ◽

Inhibitor Of Apoptosis ◽

Alternative Mechanism ◽

Caspase Activity ◽

Selective Activation ◽

Antiapoptotic Effect ◽

Caspase Inhibition ◽

Tnf Α ◽

Antiapoptotic Activity ◽

Induced Apoptosis

ABSTRACT The antiapoptotic properties of the inhibitor of apoptosis (IAP) family of proteins have been linked to caspase inhibition. We have previously described an alternative mechanism of XIAP inhibition of apoptosis that depends on the selective activation of JNK1. Here we report that two other members of the IAP family, NAIP and ML-IAP, both activate JNK1. Expression of catalytically inactive JNK1 blocks NAIP and ML-IAP protection against ICE- and TNF-α-induced apoptosis, indicating that JNK1 activation is necessary for the antiapoptotic effect of these proteins. The MAP3 kinase, TAK1, appears to be an essential component of this antiapoptotic pathway since IAP-mediated activation of JNK1, as well as protection against TNF-α- and ICE-induced apoptosis, is inhibited when catalytically inactive TAK1 is expressed. In addition, XIAP, NAIP, and JNK1 bind to TAK1. Importantly, expression of catalytically inactive TAK1 did not affect XIAP inhibition of caspase activity. These data suggest that XIAP's antiapoptotic activity is achieved by two separate mechanisms: one requiring TAK1-dependent JNK1 activation and the second involving caspase inhibition.

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