Nicorandil potentiates sodium butyrate induced preconditioning of neurons and enhances their survival upon subsequent treatment with H2O2

Tabeshmehr, Parisa; Husnain, Haider Kh; Salmannejad, Mahin; Sani, Mahsa; Hosseini, Seyed Mojtaba; Shirazi, Mohammad Hossein Khorraminejad

doi:10.1186/s40035-017-0097-1

Cited by 17 publications

(11 citation statements)

References 44 publications

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“…24 For combined treatment, Nico was added to the culture media with concentrations of 12 µM on day 3 after start of NaB treatment as described earlier. 24 LY294002 at the final concentration of 10 µM for 48 hours used as a phosphatidylinositol-3 kinase (PI3K) inhibitor 25 and also AR03 (cat #2136; Axon Medchem, Groningen, The Netherlands) at the concentration of 1 µM as specific APE1 inhibitor. 26 These inhibitory small molecules were used to loss of function and confirm their specific roles in each cascade.…”

Section: Methodsmentioning

confidence: 99%

“…24 For combined treatment, Nico was added to the culture media with concentrations of 12 µM on day 3 after start of NaB treatment as described earlier. 24 For combined treatment, Nico was added to the culture media with concentrations of 12 µM on day 3 after start of NaB treatment as described earlier.…”

Section: Small Molecules Treatmentmentioning

confidence: 99%

“…[19][20][21][22] The harsh cytokine-rich microenvironment in the ischemic area, accentuated by the infiltrating inflammatory cells and debris of the necrotizing host tissue causes extensive death of the transplanted cells. 24 Molecular studies revealed a possible activation of apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor (Ref) cascade in the preconditioned cells. 23 We have previously shown that concomitant pretreatment of neural stem cells (NSCs) with small molecules sodium butyrate (NaB) and nicorandil (Nico) preconditioned the cells to significantly enhance their survival under oxidative stress in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Preconditioned neurons with NaB and nicorandil, a favorable source for stroke cell therapy

Hosseini

Ziaee

Haider³

et al. 2018

J of Cellular Biochemistry

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Poor survival of stem cells in the harsh microenvironment at the site of stroke, especially during acute phase of injury, remains a serious obstacle to achieve the desired prognosis. We hypothesized that combined treatment of neural stem cells (NSCs) with small molecules would precondition them to become robust and survive better as compared with the native nonpreconditioned cells. Mouse ganglionic NSCs were isolated, cultured, and characterized. The cells were preconditioned by treatment with sodium butyrate (NaB) and nicorandil (Nico) and transplanted in an experimentally induced stroke model. Sham-operated animals without treatment or animals with experimental stroke treated with basal medium, native NSCs, NSCs preconditioned with NaB or Nico alone were used as controls. The tissue samples and cells with different treatments were used to measure brain-tissue-derived neurotrophic factor (BDNF) level and the activity of phosphatidylinositol-3 kinase (PI3K), apurinic/apyrimidinic endonuclease 1 (APE1), and nuclear factor-κB (NF-κB) p50 both in vitro and in vivo, respectively. Additionally, survival of the cells and recovery indices for stroke were studied. The combined treatment with NaB + Nico resulted in increased BDNF level and higher PI3K, APE1, and the downstream NF-κB activation, which were blocked by pretreatment with their respective inhibitors. Donor cell survival increased postengraftment as assessed by 5-bromo-2'-deoxyuridine immunostaining and reduced Terminal deoxynucleotide transferase dUTP Nick End Labeling positivity at the site of engraftment. There was reduction in proinflammatory cytokines and infiltration of both GFAP and CD68 at the injury site. There was reduction in the infarct size and neurological function was preserved in the preconditioned cell treatment group. Our preconditioning approach with small molecules effectively improved the survival as well as functionality of NSCs.

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Section: Methodsmentioning

confidence: 99%

Section: Small Molecules Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preconditioned neurons with NaB and nicorandil, a favorable source for stroke cell therapy

Hosseini

Ziaee

Haider³

et al. 2018

J of Cellular Biochemistry

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“…Then, 5 × 10 5 cells were collected and incubated with Annexin V-FITC for 5 min at room temperature in the dark. Afterward, the cells were detected by flow cytometry using Flow Cytometer laser 488 nm (Becton Dickinson, NJ) and analyzed with FlowJo™ Software [31].…”

Section: Annexin V Stainingmentioning

confidence: 99%

AICAR and nicotinamide treatment synergistically augment the proliferation and attenuate senescence-associated changes in mesenchymal stromal cells

Khorraminejad-Shirazi

Sani

Talaei‐Khozani

et al. 2020

Stem Cell Res Ther

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Background: Mesenchymal stromal cell (MSC) stemness capacity diminishes over prolonged in vitro culture, which negatively affects their application in regenerative medicine. To slow down the senescence of MSCs, here, we have evaluated the in vitro effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, and nicotinamide (NAM), an activator of sirtuin1 (SIRT1). Methods: Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10. Cell proliferation, differentiation capacity, level of apoptosis and autophagy, morphological changes, total cellular reactive oxygen species (ROS), and activity of mTORC1 and AMPK were compared among different treatment groups. Results: MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both. Treatment with AICAR or NAM led to decreased expression of β-galactosidase, reduced accumulation of dysfunctional lysosomes, and characteristic morphologic features of young MSCs. Furthermore, while NAM administration could significantly reduce the total cellular ROS in aged MSCs, AICAR treatment did not. Moreover, AICAR-treated cells possess a high proliferation capacity; however, they also show the highest level of cellular apoptosis. The observed effects of AICAR and NAM were in light of the attenuated mTORC1 activity and increased AMPK activity and autophagy. Conclusions: Selective inhibition of mTORC1 by AICAR and NAM boosts autophagy, retains MSCs' self-renewal and multi-lineage differentiation capacity, and postpones senescence-associated changes after prolonged in vitro culture. Additionally, co-administration of AICAR and NAM shows an additive or probably a synergistic effect on cellular senescence.

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“…Hence, it is imperative to reinforce the donor cell to withstands the rigors of the microenvironment of the infarcted site by optimizing cell engraftment and this without increasing complications [82]. Authors had shown in stroke [83] and in myocardial infarction [80], that priming cells prior transplantation with cytokines to a state of "readiness" by stimulating their survival pathways will fortify cell engraftment leading to enhance survival and to overcome numbers of problems occurring during the post engraftment period.…”

Section: Different Cell Doses Have Been Used In the Includedmentioning

confidence: 99%

Stem Cell Therapy for Ischemic Stroke: From Bench to Bedside

De¹,

De²,

Hachimi-Idrissi³

2018

Int J Crit Care Emerg Med

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Introduction: Every year ischemic stroke takes many lives and leaves millions of people with neurological deficits. Currently the only approved therapy is recombinant tissue plasminogen activator, which should be administered within a narrow time window of 4.5 hours. Stem cell therapy was first initiated in several preclinical studies with promising results and lately in some clinical trials. Our research consists of 2 systematic reviews where preclinical and clinical studies were pooled. We provide a systemic review of the evidence of efficacy of cell-based therapy in both preclinical and clinical setting. Materials and methodology: After screening of databases, 76 studies were included in our systematic review of studies in rodent stroke models and 4 randomized clinical trials were used for the systematic review of studies in humans. After data extraction and assessment of study quality, the pooled effects were calculated using Revman5. Results: Stem cell therapy has a positive effect on behavior and histological outcome in rodent stroke models. These results are in line with previously conducted meta-analyses. This improvement in rodents is not translated into clinical trials in humans. Pooled study data of the randomized controlled clinical trials did show a significant improvement in neurologic outcome, but not in functional recovery. Conclusion: Study quality is pointed out as one of the major reasons for failed translation of preclinical evidence to clinic. Large, well-designed preclinical trials are urgently needed. Good preclinical research is necessary to determine the optimal route of administration, the optimal cell dose and type and the most accurate administration time of the stem cells.

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Nicorandil potentiates sodium butyrate induced preconditioning of neurons and enhances their survival upon subsequent treatment with H2O2

Cited by 17 publications

References 44 publications

Preconditioned neurons with NaB and nicorandil, a favorable source for stroke cell therapy

Preconditioned neurons with NaB and nicorandil, a favorable source for stroke cell therapy

AICAR and nicotinamide treatment synergistically augment the proliferation and attenuate senescence-associated changes in mesenchymal stromal cells

Stem Cell Therapy for Ischemic Stroke: From Bench to Bedside

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