Mitochondrial Nitric Oxide Mediates Decreased Vulnerability of Hippocampal Neurons from Immature Animals to NMDA

Marks, Jeremy D.; Boriboun, Chan; Wang, Janice

doi:10.1523/jneurosci.1450-05.2005

Cited by 48 publications

(45 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may provide an explanation for the modulation of Ca 2ϩ homeostasis in ER by TABM. Several studies have provided evidence that a mild decrease in mitochondrial membrane potential impairs the uptake of Ca 2ϩ , in turn, protecting neurons from cell death (Stout et al, 1998;Mattiasson et al, 2003;Pivovarova et al, 2004;Marks et al, 2005). Our results also demonstrated that TABM decreased mitochondrial membrane potential.…”

Section: Discussionsupporting

confidence: 79%

Ester Derivatives of Tournefolic Acid B Attenuate N-Methyl-d-aspartate-Mediated Excitotoxicity in Rat Cortical Neurons

Wang¹,

Pan²,

Lin³

et al. 2005

Mol Pharmacol

View full text Add to dashboard Cite

The effects of tournefolic acid B (TAB) and two ester derivatives, TAB methyl ester (TABM) and TAB ethyl ester (TABE), on N-methyl-D-aspartate (NMDA)-mediated excitotoxicity and the underlying mechanisms were investigated. Treatment with 50 M NMDA elicited neuronal death by 48.7 Ϯ 5.1%, coinciding with the appearance of injured morphology. TABM (50 M) attenuated the NMDA-induced cell death by 60.9 Ϯ 19.7%, and to a lesser extent by TABE. The NMDA-mediated activation of calpain was not affected by TABM and TABE, as determined by the cleavage of ␣-spectrin. NMDA increased the activity of caspases 2, 3, 6, 8, and 9 and reached the maximum after 8-h treatment. TABM and TABE abrogated NMDA-induced activation of caspases 2, 3, 6, and 8 by approximately 80 to 90% and 50 to 60%, respectively, and to a higher extent for caspase 9. TABM and TABE also blocked the NMDA-mediated activation of caspase 12. Furthermore, TABM and TABE eliminated the NMDA-induced accumulation of superoxide anion (O 2 . ). NMDA evoked significant depolarization of mitochondria, whereas TABM elicited a mild decrease of mitochondrial membrane potential as determined by tetramethylrhodamine methyl ester perchlorate. NMDA treatment induced elevation of Ca 2ϩ levels in cytosol, endoplasmic reticulum (ER), and mitochondria. TABM (50 M) significantly diminished the NMDA-induced elevation of Ca 2ϩ levels in mitochondria and ER but not cytosol. Therefore, TABM decreased mitochondrial membrane potential and attenuated the NMDA-mediated Ca 2ϩ -loading in ER and mitochondria. These events subsequently eliminated the accumulation of O 2. and blocked the activation of caspase cascade, thereby conferring their neuroprotective effects on NMDA-mediated excitotoxicity.

show abstract

Section: Discussionsupporting

confidence: 79%

Ester Derivatives of Tournefolic Acid B Attenuate N-Methyl-d-aspartate-Mediated Excitotoxicity in Rat Cortical Neurons

Wang¹,

Pan²,

Lin³

et al. 2005

Mol Pharmacol

View full text Add to dashboard Cite

show abstract

“…Consistent with this is the finding that ODQ does not decrease excitotoxic effects of NO. 27 Thus, SNOC-induced mitochondrial fission in neurons appears to be independent of the GC pathway.…”

Section: Discussionmentioning

confidence: 98%

Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons

et al. 2006

View full text Add to dashboard Cite

Mitochondrial dysfunction is an underpinning event in many neurodegenerative disorders. Less clear, however, is how mitochondria become injured during neuronal demise. Nitric oxide (NO) evokes rapid mitochondrial fission in cortical neurons. Interestingly, proapoptotic Bax relocates from the cytoplasm into large foci on mitochondrial scission sites in response to nitrosative stress. Antiapoptotic Bcl-xL does not prevent mitochondrial fission despite its ability to block Bax puncta formation on mitochondria and to mitigate neuronal cell death. Mitofusin 1 (Mfn1) or dominant-negative dynamin-related protein 1 K38A (Drp1 k38A ) inhibits mitochondrial fission and Bax accumulation on mitochondria induced by exposure to an NO donor. Although NO is known to cause a bioenergetic crisis, lowering ATP by glycolytic or mitochondrial inhibitors neither induces mitochondrial fission nor Bax foci formation on mitochondria. Taken together, these data indicate that the mitochondrial fission machinery acts upstream of the Bcl-2 family of proteins in neurons challenged with nitrosative stress.

show abstract

“…After incubation, cells were washed two times with 0.2% (w/v) BSA in PBS, and fluorescence was immediately measured in a plate reader at an excitation wavelength of 549 nm and an emission wavelength of 575 nm. In some experiments, the digital image analysis method (22,23) was used to estimate ⌬ m in individual fibroblasts (see below). This approach allowed us to take variations in the electrochemical potential across cellular plasma membranes (⌬ p ) (22) into consideration.…”

Section: /Clmentioning

confidence: 99%

The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective Channel That Modulates Membrane Potential

Antonenkov

Isomursu

Mennerich

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Mitochondrial Nitric Oxide Mediates Decreased Vulnerability of Hippocampal Neurons from Immature Animals to NMDA

Cited by 48 publications

References 84 publications

Ester Derivatives of Tournefolic Acid B Attenuate N-Methyl-d-aspartate-Mediated Excitotoxicity in Rat Cortical Neurons

Ester Derivatives of Tournefolic Acid B Attenuate N-Methyl-d-aspartate-Mediated Excitotoxicity in Rat Cortical Neurons

Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons

The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective Channel That Modulates Membrane Potential

Contact Info

Product

Resources

About