Neuroprotective effects of a novel carnosine-hydrazide derivative on hippocampal CA1 damage after transient cerebral ischemia

Noguchi, Kei; Ali, Taha F. S.; Miyoshi, Junko; Orito, Kensuke; Negoto, Tetsuya; Biswas, Tanima; Taira, Naomi; Koga, Ryoko; Okamoto, Yoshinari; Fujita, Mikako; Otsuka, Masami; Morioka, Motohiro

doi:10.1016/j.ejmech.2018.11.060

Cited by 10 publications

(10 citation statements)

References 38 publications

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“…Thanks to its antioxidant, pH-buffering, and metal ion-chelating properties, combined with good tolerability and safety profile, carnosine is commonly used as dietary supplement [163]. Carnosine and its derivatives have been reported to have a potential for the treatment of several pathologies, including brain ischemia [164,165,166,167,168,169]. Carnosine is also able to reduce MCs release of histamine [170].…”

Section: Mcs Modulation: a Promising Strategy In Stroke Treatmentmentioning

confidence: 99%

The Role of Mast Cells in Stroke

Parrella

Porrini

Benarese

et al. 2019

Cells

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Mast cells (MCs) are densely granulated perivascular resident cells of hematopoietic origin. Through the release of preformed mediators stored in their granules and newly synthesized molecules, they are able to initiate, modulate, and prolong the immune response upon activation. Their presence in the central nervous system (CNS) has been documented for more than a century. Over the years, MCs have been associated with various neuroinflammatory conditions of CNS, including stroke. They can exacerbate CNS damage in models of ischemic and hemorrhagic stroke by amplifying the inflammatory responses and promoting brain–blood barrier disruption, brain edema, extravasation, and hemorrhage. Here, we review the role of these peculiar cells in the pathophysiology of stroke, in both immature and adult brain. Further, we discuss the role of MCs as potential targets for the treatment of stroke and the compounds potentially active as MCs modulators.

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Section: Mcs Modulation: a Promising Strategy In Stroke Treatmentmentioning

confidence: 99%

The Role of Mast Cells in Stroke

Parrella

Porrini

Benarese

et al. 2019

Cells

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“…It is precisely because of the neuronal origin and the ability to acquire functional characteristics; PC12 cells are diffusely applied in the researches about ischemic stroke to expand our knowledge on pathological process. 25,26 In our study, PC12 cells were stimulated by hypoxia to establish an in vitro cell model of cerebral ischemia, and then the roles of TPP and the underlying mechanism were explored.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Typhae pollen polysaccharides protect hypoxia-induced PC12 cell injury via regulation of miR-34a/SIRT1

Wang

Tang

et al. 2020

Int J Immunopathol Pharmacol

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This current research was performed to investigate the role of typhae pollen polysaccharides (TPP) in hypoxia-treated PC12 cell which was an in vitro cell model of cerebral ischemia. Hypoxia-treated cells were treated with TPP for 12 h. Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2 5-diphenyl-2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. Cell apoptotic proteins and PI3K/AKT and Ras/Raf/MEK/ERK signal pathway–associated proteins were also examined by western blot. Furthermore, abnormal expression of miR-34a and silent information regulator 1 (SIRT1) was achieved by transfection. Besides, the expression of miR-34a and SIRT1 was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of SIRT1 was detected by qRT-PCR and western blot. The relationship between miR-34a and SIRT1 was verified by luciferase assay. We found that TPP enhanced cell viability and inhibited apoptosis in hypoxia-treated PC12 cells. Moreover, TPP increased the accumulated levels of Bcl-2 while decreased expression of Bax, cleaved Caspase-3, and cleaved PARP. TPP downregulated miR-34a expression while induced by hypoxia. Further results showed that miR-34a overexpression reversed the results led by TPP in cell viability, apoptosis, and its related proteins. In addition, SIRT1 was upregulated by TPP and was verified to be a target of miR-34a. Silence of SIRT1 led to the opposite results led by TPP. In the end, TPP activated PI3K/AKT and Ras/Raf/MEK/ERK signal pathways. In conclusion, TPP plays important roles in regulating cell viability and apoptosis in hypoxia-treated PC12 cells via modulating miR-34a/SIRT1, as well as activating PI3K/AKT and Ras/Raf/MEK/ERK signal pathways.

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“…To further prove the causal relationship between 4-HNE, pancreas disruption, hyperglycaemia and vascular alterations, and to kick out unspecific side effects of 4-HNE, we observed the pancreas morphology and hyaloid vasculature under 4-HNE incubation and checked out if the rescue effect existed via RCS scavenger and anti-hyperglycaemic intervention. l -Carnosine was chosen as an antioxidant and scavenger of RCS, which protects tissue from 4-HNE induced oxidative damage [ 42 ]. Besides, PK11195 was selected as an anti-hyperglycaemic drug, which showed strong effects on decreasing glucose level in hyperglycaemic zebrafish larvae [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

Elevated 4-hydroxynonenal induces hyperglycaemia via Aldh3a1 loss in zebrafish and associates with diabetes progression in humans

et al. 2020

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Increased methylglyoxal (MG) formation is associated with diabetes and its complications. In zebrafish, knockout of the main MG detoxifying system Glyoxalase 1, led to limited MG elevation but significantly elevated aldehyde dehydrogenases (ALDH) activity and aldh3a1 expression, suggesting the compensatory role of Aldh3a1 in diabetes. To evaluate the function of Aldh3a1 in glucose homeostasis and diabetes, aldh3a1 −/− zebrafish mutants were generated using CRISPR-Cas9. Vasculature and pancreas morphology were analysed by zebrafish transgenic reporter lines. Corresponding reactive carbonyl species (RCS), glucose, transcriptome and metabolomics screenings were performed and ALDH activity was measured for further verification. Aldh3a1 −/− zebrafish larvae displayed retinal vasodilatory alterations, impaired glucose homeostasis, which can be aggravated via pdx1 silencing induced hyperglycaemia. Unexpectedly, MG was not altered, but 4-hydroxynonenal (4-HNE), another prominent lipid peroxidation RCS exhibited high affinity with Aldh3a1, was increased in aldh3a1 mutants. 4-HNE was responsible for the retinal phenotype via pancreas disruption induced hyperglycaemia and can be rescued via l -Carnosine treatment. Furthermore, in type 2 diabetic patients, serum 4-HNE was increased and correlated with disease progression. Thus, our data suggest impaired 4-HNE detoxification and elevated 4-HNE concentration as biomarkers but also the possible inducers for diabetes, from genetic susceptibility to the pathological progression.

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Neuroprotective effects of a novel carnosine-hydrazide derivative on hippocampal CA1 damage after transient cerebral ischemia

Cited by 10 publications

References 38 publications

The Role of Mast Cells in Stroke

The Role of Mast Cells in Stroke

RETRACTED: Typhae pollen polysaccharides protect hypoxia-induced PC12 cell injury via regulation of miR-34a/SIRT1

Elevated 4-hydroxynonenal induces hyperglycaemia via Aldh3a1 loss in zebrafish and associates with diabetes progression in humans

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