Tags

Type your tag names separated by a space and hit enter

NF-kappaB activation is associated with homocysteine-induced injury in Neuro2a cells.
BMC Neurosci. 2008 Jul 07; 9:62.BN

Abstract

BACKGROUND

Perinatal exposure to hyperhomocysteinemia might disturb neurogenesis during brain development and growth. Also, high levels of homocysteine trigger neurodegeneration in several experimental models. However, the putative mechanisms of homocysteine-induced toxicity in the developing nervous system have poorly been elucidated. This study was aimed to investigate homocysteine effects in undifferentiated neuroblastoma cells, Neuro2a.

RESULTS

A 4 h exposure to homocysteine in a concentration range of 10-100 microM did not affect cell viability and ROS production in Neuro2a cell cultures. Instead, ROS levels were increased by two-three folds in cells treated with 250 microM and 500 microM homocysteine, respectively, in comparison with control cells. Also, the highest homocysteine dose significantly reduced the viable cell number by 40%. Notably, the treatment with homocysteine (250 microM-500 microM) in the presence of antioxidants, such as N-acetylcysteine and IRFI 016, a synthetic alpha-tocopherol analogue, recovered cell viability and significantly reduced homocysteine-evoked increases in ROS production. Moreover, antioxidants, particularly IRFI 016, were able to counteract NF-kappaB activation induced by 250 microM homocysteine. Cell treatment with 250 microM homocysteine also triggered the onset of apoptosis, as demonstrated by the increased expression of early apoptotic markers such as Bax, caspase-3 and p53. In contrast, Bcl2 expression was not affected by homocysteine exposure. Interestingly, the specific inhibition of NF-kappaB nuclear translocation by the synthetic peptide SN50 was able to almost completely suppress the homocysteine-evoked rises in pro-apoptotic protein expression as well as in caspase-3 activity. Further, also IRFI 016 and N-acetylcysteine were able to significantly reduce caspase-3 activation induced by homocysteine treatment.

CONCLUSION

These observations suggest an involvement of redox state alterations and activated NF-kappaB in apoptosis onset triggered by homocysteine in neuroblastoma cells Neuro2a. However, further investigations are needed to characterize molecular events involved in the NF-kappaB activation induced by homocysteine.

Authors+Show Affiliations

Department of Biochemical, Physiological and Nutritional Sciences, University of Messina - Messina, Italy. nadiaferlazzo@email.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18606001

Citation

Ferlazzo, Nadia, et al. "NF-kappaB Activation Is Associated With Homocysteine-induced Injury in Neuro2a Cells." BMC Neuroscience, vol. 9, 2008, p. 62.
Ferlazzo N, Condello S, Currò M, et al. NF-kappaB activation is associated with homocysteine-induced injury in Neuro2a cells. BMC Neurosci. 2008;9:62.
Ferlazzo, N., Condello, S., Currò, M., Parisi, G., Ientile, R., & Caccamo, D. (2008). NF-kappaB activation is associated with homocysteine-induced injury in Neuro2a cells. BMC Neuroscience, 9, 62. https://doi.org/10.1186/1471-2202-9-62
Ferlazzo N, et al. NF-kappaB Activation Is Associated With Homocysteine-induced Injury in Neuro2a Cells. BMC Neurosci. 2008 Jul 7;9:62. PubMed PMID: 18606001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NF-kappaB activation is associated with homocysteine-induced injury in Neuro2a cells. AU - Ferlazzo,Nadia, AU - Condello,Salvatore, AU - Currò,Monica, AU - Parisi,Giulia, AU - Ientile,Riccardo, AU - Caccamo,Daniela, Y1 - 2008/07/07/ PY - 2008/03/19/received PY - 2008/07/07/accepted PY - 2008/7/9/pubmed PY - 2008/8/30/medline PY - 2008/7/9/entrez SP - 62 EP - 62 JF - BMC neuroscience JO - BMC Neurosci VL - 9 N2 - BACKGROUND: Perinatal exposure to hyperhomocysteinemia might disturb neurogenesis during brain development and growth. Also, high levels of homocysteine trigger neurodegeneration in several experimental models. However, the putative mechanisms of homocysteine-induced toxicity in the developing nervous system have poorly been elucidated. This study was aimed to investigate homocysteine effects in undifferentiated neuroblastoma cells, Neuro2a. RESULTS: A 4 h exposure to homocysteine in a concentration range of 10-100 microM did not affect cell viability and ROS production in Neuro2a cell cultures. Instead, ROS levels were increased by two-three folds in cells treated with 250 microM and 500 microM homocysteine, respectively, in comparison with control cells. Also, the highest homocysteine dose significantly reduced the viable cell number by 40%. Notably, the treatment with homocysteine (250 microM-500 microM) in the presence of antioxidants, such as N-acetylcysteine and IRFI 016, a synthetic alpha-tocopherol analogue, recovered cell viability and significantly reduced homocysteine-evoked increases in ROS production. Moreover, antioxidants, particularly IRFI 016, were able to counteract NF-kappaB activation induced by 250 microM homocysteine. Cell treatment with 250 microM homocysteine also triggered the onset of apoptosis, as demonstrated by the increased expression of early apoptotic markers such as Bax, caspase-3 and p53. In contrast, Bcl2 expression was not affected by homocysteine exposure. Interestingly, the specific inhibition of NF-kappaB nuclear translocation by the synthetic peptide SN50 was able to almost completely suppress the homocysteine-evoked rises in pro-apoptotic protein expression as well as in caspase-3 activity. Further, also IRFI 016 and N-acetylcysteine were able to significantly reduce caspase-3 activation induced by homocysteine treatment. CONCLUSION: These observations suggest an involvement of redox state alterations and activated NF-kappaB in apoptosis onset triggered by homocysteine in neuroblastoma cells Neuro2a. However, further investigations are needed to characterize molecular events involved in the NF-kappaB activation induced by homocysteine. SN - 1471-2202 UR - https://www.unboundmedicine.com/medline/citation/18606001/NF_kappaB_activation_is_associated_with_homocysteine_induced_injury_in_Neuro2a_cells_ L2 - https://bmcneurosci.biomedcentral.com/articles/10.1186/1471-2202-9-62 DB - PRIME DP - Unbound Medicine ER -