Orexin-A regulates cell apoptosis in human H295R adrenocortical cells via orexin receptor type 1 through the AKT signaling pathway

Chang, Xin; Yang, Zhao; Ju, Shujing; Guo, Lei

doi:10.3892/mmr.2015.4381

Cited by 5 publications

(4 citation statements)

References 38 publications

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“… 16 Orexin-A increases proliferation and decreases caspase-3 activity in H295R adrenocortical cells. 17 To the best of our knowledge, this study is the first to evaluate the neuroprotective effects of Orexin-A in H 2 O 2 -treated SH-SY5Y cells. The effects of increasing concentrations of Orexin-A on the H 2 O 2 -induced decrease in SH-SY5Y cell viability were evaluated.…”

Section: Discussionmentioning

confidence: 92%

Orexin-A protects SH-SY5Y cells against H₂O₂-induced oxidative damage via the PI3K/MEK_1/2/ERK_1/2 signaling pathway

Wang

Yang

Cheng

et al. 2018

Int J Immunopathol Pharmacol

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Orexin-A elicits multiple potent effects on a variety of tumor cells via different signaling pathways. However, it is unknown whether it has a neuroprotective effect on SH-SY5Y human neuroblastoma cells. This study investigated the neuroprotective effect of Orexin-A against hydrogen peroxide (H2O2)-induced oxidative damage in SH-SY5Y cells and the underlying mechanism. H2O2 treatment decreased the viability of SH-SY5Y cells, induced apoptosis, and decreased superoxide dismutase activity. Orexin-A attenuated these effects, indicating that it protects SH-SY5Y cells against H2O2-induced oxidative damage. Pre-treatment with Orexin-A also attenuated H2O2-induced increases in phosphorylation of MEK1/2 and ERK1/2. Moreover, these effects of Orexin-A were reduced in the presence of the PI3K inhibitor LY294002. Finally, pre-treatment with LY294002 abrogated attenuation of the H2O2-induced decrease in cell viability and increase in caspase-3/7 activity by Orexin-A. These results show that the PI3K/MEK1/2/ERK1/2 signaling pathway is involved in the neuroprotective effects of Orexin-A against H2O2-induced oxidative damage in SH-SY5Y cells. Our findings provide insight into the neuroprotective effects of Orexin-A and the underlying mechanism, which will be useful for the treatment of nervous system diseases.

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Section: Discussionmentioning

confidence: 92%

Orexin-A protects SH-SY5Y cells against H₂O₂-induced oxidative damage via the PI3K/MEK_1/2/ERK_1/2 signaling pathway

Wang

Yang

Cheng

et al. 2018

Int J Immunopathol Pharmacol

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“…Moreover, it was reported that orexin A increased the mRNA and protein expression levels of 3β-HSD and cortisol secretion by H295R cells in a dose-dependent manner, with 1 μM of orexin A showing the maximal effect. Of note, the effects were partly blocked by an OX1R antagonist [ 41 , 42 ]. These results suggest that orexin enhances a wide range of steroidogenic enzymes that are involved in the synthesis of mineralocorticoids and glucocorticoids.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells

Soejima

Iwata

Nishioka

et al. 2023

IJMS

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Orexins are neuropeptides that play important roles in sleep-wake regulation and food intake in the central nervous system, but their receptors are also expressed in peripheral tissues, including the endocrine system. In the present study, we investigated the functions of orexin in adrenal steroidogenesis using human adrenocortical H295R cells by focusing on its interaction with adrenocortical bone morphogenetic proteins (BMPs) that induce adrenocortical steroidogenesis. Treatment with orexin A increased the mRNA levels of steroidogenic enzymes including StAR, CYP11B2, CYP17, and HSD3B1, and these effects of orexin A were further enhanced in the presence of forskolin. Interestingly, orexin A treatment suppressed the BMP-receptor signaling detected by Smad1/5/9 phosphorylation and Id-1 expression through upregulation of inhibitory Smad7. Orexin A also suppressed endogenous BMP-6 expression but increased the expression of the type-II receptor of ActRII in H295R cells. Moreover, treatment with BMP-6 downregulated the mRNA level of OX1R, but not that of OX2R, expressed in H295R cells. In conclusion, the results indicate that both orexin and BMP-6 accelerate adrenocortical steroidogenesis in human adrenocortical cells; both pathways mutually inhibit each other, thereby leading to a fine-tuning of adrenocortical steroidogenesis.

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“…Эта реакция выражена при применении орексина А в концентрации 1 мкМ. Аппликация орексина А приводила к усилению пролиферации клеток, выработки кортизола и увеличению экспрессии мРНК и белка 3-бета-гидроксистероиддегидрогеназы (3β-HSD) в клетках NCI-H295R; однако эти эффекты частично блокировались антагонистом рецептора OX1R [10].…”

Section: т 23 №unclassified

Tumor cell apoptosis mediated by the orexins

et al. 2021

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Orexins A and B are neuropeptides synthesized by a population of lateral hypothalamic neurons. Orexin’s physiological function consists mainly in regulating the sleep-wake cycle, eating behavior, and energy homeostasis. Axons of orexin-containing neurons are projected onto many structures of brain and spinal cord, thus providing a variety of their physiological effects. Moreover, the components of the orexinergic system are identified in various peripheral organs and tissues. The effects of orexins are mediated via two receptors (OX1R and OX2R) coupled with G-proteins (GPCRs). The classical signal transmission pathway through orexin receptors in neuronal cells includes an increase of the intracellular calcium as a result of the opening of TRPC membrane channels and IP3 endoplasmic reticulum (ER) channels. In addition to the classic orexin receptors signaling, there is an alternative pathway. Signal transmission through the alternative pathway leads to apoptosis of tumor cells. This pathway is probably due to the structural feature of orexin receptors compared to other GPCRs — the presence of a tyrosine-based immunoreceptor inhibition motif (ITIM). Such motifs are not limited to GPCRs, but are a hallmark of immuno-inhibiting receptors on lymphoid and myeloid cells. ITIM recruits either SHP1 and SHP2 protein tyrosine phosphatases or SHIP1 and SHIP2 inositol phosphatases, to mediate negative signal transduction. A further mechanism of the so-called orexin-induced apoptosis seems to include the p38/MAPK phosphorylation and the cytochrome c releasing from mitochondria, followed by activation of caspases 3 and 7 and cell death. It should be emphasized that this alternative pathway is present only in certain types of tumor cells. This review summarizes the available data on orexin-induced apoptosis of tumor cells from intestines, pancreas, stomach, prostate, endometrium, adrenal glands and glia, and also considers possible mechanisms for its implementation.

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Orexin-A regulates cell apoptosis in human H295R adrenocortical cells via orexin receptor type 1 through the AKT signaling pathway

Cited by 5 publications

References 38 publications

Orexin-A protects SH-SY5Y cells against H₂O₂-induced oxidative damage via the PI3K/MEK_1/2/ERK_1/2 signaling pathway

Orexin-A protects SH-SY5Y cells against H₂O₂-induced oxidative damage via the PI3K/MEK_1/2/ERK_1/2 signaling pathway

Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells

Tumor cell apoptosis mediated by the orexins

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Orexin-A regulates cell apoptosis in human H295R adrenocortical cells via orexin receptor type 1 through the AKT signaling pathway

Cited by 5 publications

References 38 publications

Orexin-A protects SH-SY5Y cells against H2O2-induced oxidative damage via the PI3K/MEK1/2/ERK1/2 signaling pathway

Orexin-A protects SH-SY5Y cells against H2O2-induced oxidative damage via the PI3K/MEK1/2/ERK1/2 signaling pathway

Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells

Tumor cell apoptosis mediated by the orexins

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Orexin-A protects SH-SY5Y cells against H₂O₂-induced oxidative damage via the PI3K/MEK_1/2/ERK_1/2 signaling pathway

Orexin-A protects SH-SY5Y cells against H₂O₂-induced oxidative damage via the PI3K/MEK_1/2/ERK_1/2 signaling pathway