Retroviral expression of arginine decarboxylase attenuates oxidative burden in mouse cortical neural stem cells

Kiran Kumar Bokara, Ki Hyo Kwon, Yoonmi Nho, Won Taek Lee, Kyung Ah Park, Jongeun Lee

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Neural stem cells (NSCs) have the potential to integrate seamlessly into the host tissues, and the development of potential stem cells resistant to stress injury is an elusive goal for efficient therapeutic application. Oxidative injury induces cellular and nuclear damages and the balanced regulation of reactive oxygen species is of critical significance for stem cell development, function, and survival. Agmatine, an endogenous primary amine and a novel neuromodulator synthesized from the decarboxylation of l-arginine catalyzed by arginine decarboxylase (ADC), has been reported to possess neuroprotective properties. In the present study, we determined whether the expression of ADC in NSCs can prevent the cells from oxidative injury. Retrovirus expressing human (ADC), (vhADC) was generated using a pLXSN vector. Cortical NSCs were infected with vhADC and subjected to H2O 2 injury (200 μM for 15 h). Reverse transcriptase-polymerase chain reaction and immunocytochemical staining revealed that hADC mRNA and protein were highly expressed in the vhADC-infected NSCs (ADC-NSCs). High performance liquid chromatography (HPLC) analysis confirmed high concentration of agmatine in the ADC-NSCs, when exposed to H2O2 injury. Lactate dehydrogenase leakage and intracellular reactive oxygen species formation were about 2-fold reduced in ADC-NSCs when compared with control NSCs and NSCs infected with mock vector (P < 0.05). DNA fragmentation, chromatin condensation, and expression of apoptotic proteins such as p53, bax, and caspase-3 cleavage were significantly decreased in ADC-NSCs (P < 0.05), suggesting the prevention of apoptotic cell death following H2O 2 injury. Our study demonstrates that overexpression of ADC is an effective novel approach to protect stem cells from oxidative damage.

Original languageEnglish
Pages (from-to)527-537
Number of pages11
JournalStem Cells and Development
Volume20
Issue number3
DOIs
Publication statusPublished - 2011 Mar 1

Fingerprint

Neural Stem Cells
Wounds and Injuries
Agmatine
Stem Cells
Reactive Oxygen Species
arginine decarboxylase
Decarboxylation
DNA Fragmentation
Retroviridae
Reverse Transcriptase Polymerase Chain Reaction
L-Lactate Dehydrogenase
Caspase 3
Chromatin
Amines
Neurotransmitter Agents
Arginine
Proteins
Cell Death
High Pressure Liquid Chromatography
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

Bokara, Kiran Kumar ; Kwon, Ki Hyo ; Nho, Yoonmi ; Lee, Won Taek ; Park, Kyung Ah ; Lee, Jongeun. / Retroviral expression of arginine decarboxylase attenuates oxidative burden in mouse cortical neural stem cells. In: Stem Cells and Development. 2011 ; Vol. 20, No. 3. pp. 527-537.
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Retroviral expression of arginine decarboxylase attenuates oxidative burden in mouse cortical neural stem cells. / Bokara, Kiran Kumar; Kwon, Ki Hyo; Nho, Yoonmi; Lee, Won Taek; Park, Kyung Ah; Lee, Jongeun.

In: Stem Cells and Development, Vol. 20, No. 3, 01.03.2011, p. 527-537.

Research output: Contribution to journalArticle

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