Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner

Kotova, Polina D.; Kochkina, Ekaterina N.; Lyamin, Oleg O.; Rogachevskaja, Olga A.; Korolenko, Nina P.; Ivashin, Denis S.; Bystrova, M. F.; Enukashvily, N. I.; Kolesnikov, Stanislav S.

doi:10.1016/j.ejphar.2020.173182

Cited by 11 publications

(12 citation statements)

References 35 publications

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“…A large proportion of bone trabeculars lost their normal architecture and looked like separate bone areas separated by extended spaces. This is consistent with the results of several researchers (Almarestani et al, 2011) and, according to Noguchi et al (2008), can be caused by activation of inflammation mediators, by means of which stimulation of osteoclastic formation takes place, which eventually leads to periarticular bone resorption (Kotova et al, 2020).…”

Section: Micro-ct Analysissupporting

confidence: 93%

Anti‐arthritic effect of chicken embryo tissue hydrolyzate against adjuvant arthritis in rats (X‐ray microtomographic and histopathological analysis)

Rzhepakovsky

Siddiqui

Avanesyan

et al. 2021

Food Science & Nutrition

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Section: Micro-ct Analysissupporting

confidence: 93%

Anti‐arthritic effect of chicken embryo tissue hydrolyzate against adjuvant arthritis in rats (X‐ray microtomographic and histopathological analysis)

Rzhepakovsky

Siddiqui

Avanesyan

et al. 2021

Food Science & Nutrition

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“…A large proportion of bone trabeculars lost their normal architecture and looked like separate bone areas separated by extended spaces. This is consistent with the results of several researchers [47] and, according to Noguchi et al [51] can be caused by activation of inflammation mediators, by means of which stimulation of osteoclastic formation takes place, which eventually leads to periarticular bone resorption [52].…”

Section: Micro-ct Analysissupporting

confidence: 93%

Anti-Arthritic Effect of Chicken Embryo Tissue Hydrolyzate Against Adjuvant Arthritis in Rats (X-Ray Microtomographic and Histopathological Analysis)

Rzhepakovsky¹,

Avanesyan²,

Benlidayı³

et al. 2020

Preprint

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Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Of particular interest in this regard are bioactive peptides and peptide-rich protein hydrolyzates, which represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant in rats. The anti-arthritic effect of CETH was studied on the 28th day of the experiment after two weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X-ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non-steroidal anti-inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose-dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammatory edema, inhibition of osteolysis, prevention of osteophitosis, reduction of the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents a potential theoretical strategy for the safe correction of this pathological process and, for the first time, shows that CETH may be a powerful potential nutraceutical agent or bioactive component of functional products in the treatment of rheumatoid arthritis.

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“…LY294002 is a specific inhibitor of the PI3K/Akt pathway. It inhibits the activation of PI3K and the phosphorylation of Akt by inhibiting the combination of ATP and PI3K-P85, thereby affecting the transduction of the P13K/Akt pathway [23,24]. LY294002 has similar PI3K/Akt inhibitory efficacy in all cells, but different cell models and different intervention methods have significant differences in tolerability [25,26].…”

Section: Discussionmentioning

confidence: 99%

Recombinant human erythropoietin protects long-term cultured ageing primary nerve cells by upregulating the PI3K/Akt pathway

et al. 2022

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Objective Previous studies have found that recombinant human erythropoietin (rhEPO) protects long-term cultured ageing primary nerve cells by enhancing the endogenous antioxidant capacity of cells; however, its signalling pathways are not clear. This study aimed to explore the relationship between the rhEPO and PI3K/Akt pathways in the protection of senescent nerve cells at the cellular level. Methods Primary nerve cells were cultured for 22 days to mimic the natural ageing process of nerve cells. rhEPO and LY294002 were administered as an intervention on the 11th day of culture. Western blot, immunochemistry, 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide, immunofluorescence double-labelling staining, Annexin V-FITC/PI double-labelling flow cytometry, and SA-β-gal staining experiments were used to observe the expression levels of erythropoietin receptor (EPOR) and phosphorylated Akt (p-Akt) protein and the related indices of nerve cell senescence. Results Western blot experiments showed that in ageing long-term cultured primary neurons, the EPOR and p-Akt decreased and rhEPO upregulated the expression levels of EPOR and p-Akt protein. The rest showed that the PI3K/Akt pathway blockade reduced the antioxidation capacity, cell viability, cell morphology, and ratio of apoptotic cells and senescent cells of rhEPO on ageing long-term cultured primary nerve cells. Conclusions This study explored the relationship between the rhEPO and PI3K/Akt pathways in the protection of ageing nerve cells at the cellular level and found that rhEPO protects long-term cultured ageing primary nerve cells by upregulating the PI3K/Akt pathway. These findings provide a theoretical basis and experimental evidence for the antiaeging mechanism of EPO in the nervous system.

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Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner

Cited by 11 publications

References 35 publications

Anti‐arthritic effect of chicken embryo tissue hydrolyzate against adjuvant arthritis in rats (X‐ray microtomographic and histopathological analysis)

Anti‐arthritic effect of chicken embryo tissue hydrolyzate against adjuvant arthritis in rats (X‐ray microtomographic and histopathological analysis)

Anti-Arthritic Effect of Chicken Embryo Tissue Hydrolyzate Against Adjuvant Arthritis in Rats (X-Ray Microtomographic and Histopathological Analysis)

Recombinant human erythropoietin protects long-term cultured ageing primary nerve cells by upregulating the PI3K/Akt pathway

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