scholarly journals RNAi-mediated knockdown of MTNR1B without disrupting the effects of melatonin on apoptosis and cell cycle in bovine granulose cells

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4463 ◽  
Author(s):  
Wenju Liu ◽  
Shujuan Wang ◽  
Jinxing Zhou ◽  
Xunsheng Pang ◽  
Like Wang

Melatonin is well known as a powerful free radical scavenger and exhibits the ability to prevent cell apoptosis. In the present study, we investigated the role of melatonin and its receptor MTNR1B in regulating the function of bovine granulosa cells (GCs) and hypothesized the involvement of MTNR1B in mediating the effect of melatonin on GCs. Our results showed that MTNR1B knockdown significantly promoted GCs apoptosis but did not affect the cell cycle. These results were further verified by increasing the expression of pro-apoptosis genes (BAX and CASP3), decreasing expression of the anti-apoptosis genes (BCL2 and BCL-XL) and anti-oxidant genes (SOD1 and GPX4) without affecting cell cycle factors (CCND1, CCNE1 and CDKN1A) and TP53. In addition, MTNR1B knockdown did not disrupt the effects of melatonin in suppressing the GCs apoptosis or blocking the cell cycle. Moreover, MTNR1B knockdown did not affect the role of melatonin in increasing BCL2, BCL-XL, and CDKN1A expression, or decreasing BAX, CASP3, TP53, CCND1 and CCNE1 expression. The expression of MTNR1A was upregulated after MTNR1B knockdown, and melatonin promoted MTNR1A expression with or without MTNR1B knockdown. However, despite melatonin supplementation, the expression of SOD1 and GPX4 was still suppressed after MTNR1B knockdown. In conclusion, these findings indicate that melatonin and MTNR1B are involved in BCL2 family and CASP3-dependent apoptotic pathways in bovine GCs. MTNR1A and MTNR1B may coordinate the work of medicating the appropriate melatonin responses to GCs.

2020 ◽  
Vol 10 (01) ◽  
pp. e104-e109
Author(s):  
Antonio Molina-Carballo ◽  
Antonio Emilio Jerez-Calero ◽  
Antonio Muñoz-Hoyos

AbstractMelatonin, produced in every cell that possesses mitochondria, acts as an endogenous free radical scavenger, and improves energetic metabolism and immune function, by complex molecular crosstalk with other intracellular compounds. There is greatly increasing evidence regarding beneficial effects of acute and chronic administration of high melatonin doses, in infectious, developmental, and degenerative pathologies, as an endothelial cell and every cell protectant.


1986 ◽  
Vol 41 (5) ◽  
pp. 551-556 ◽  
Author(s):  
John C. Coles ◽  
S. Naeem Ahmed ◽  
Harendra U. Mehta ◽  
John C.E. Kaufmann

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1871
Author(s):  
Rita Martín-Ramírez ◽  
Rebeca González-Fernández ◽  
Jairo Hernández ◽  
Pablo Martín-Vasallo ◽  
Angela Palumbo ◽  
...  

An excess of oxidative stress (OS) may affect several physiological processes fundamental to reproduction. SIRT1, SIRT6 and SIRT7 are involved in protection stress systems caused by OS, and they can be activated by antioxidants such as celastrol or melatonin. In this study, we evaluate SIRT1, SIRT6 and SIRT7 gene expression in cultured human granulosa-lutein (hGL) cells in response to OS inductors (glucose or peroxynitrite) and/or antioxidants. Our results show that celastrol and melatonin improve cell survival in the presence and absence of OS inductors. In addition, melatonin induced SIRT1, SIRT6 and SIRT7 gene expression while celastrol only induced SIRT7 gene expression. This response was not altered by the addition of OS inductors. Our previous data for cultured hGL cells showed a dual role of celastrol as a free radical scavenger and as a protective agent by regulating gene expression. This study shows a direct effect of celastrol on SIRT7 gene expression. Melatonin may protect from OS in a receptor-mediated manner rather than as a scavenger. In conclusion, our results show increased hGL cells survival with melatonin or celastrol treatment under OS conditions, probably through the regulation of nuclear sirtuins’ gene expression.


1993 ◽  
Vol 39 (1) ◽  
pp. 22-27 ◽  
Author(s):  
Yuji Okatani ◽  
Nobuyuki Morioka ◽  
Akihiko Wakatsuki ◽  
Yuji Nakano ◽  
Yusuke Sagara

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 433
Author(s):  
Mauro Fiorini ◽  
Veronica Crognaletti ◽  
Omar Sabry ◽  
Lorenzo Scalise ◽  
Paolo Fattori

Biomedical engineering is employing hydrogels with increasingly exciting possibilities for the treatment and regeneration of pathologically altered, degenerated, or traumatized tissues. Still, the sterilization processes may undesirably change the chemical and physical properties of hydrogels through cross-linking reactions. This work aims to characterize a new method of producing polyethylene oxide (PEO) hydrogels exploiting hydroxy-tyrosol (HT), an anti-oxidant molecule derived from olive leaf and olive oil, as a free radical scavenger to either prevent or limit gamma-ray-induced cross-linking. For this purpose, we produced hydrogels with PEO with two different buffer solutions (phosphate and citrate), varying HT concentration. We analyzed hydrogel preparations before and after gamma-ray irradiation, assessing the viscosity through rheological analysis and the chemical changes through IR analysis. We performed high-performance liquid chromatography (HPLC) analysis to measure residual HT in hydrogels after irradiation. The obtained results show that radiation-induced cross-linking and increase in viscosity of PEO hydrogels can be prevented by tailoring the concentration of HT as a free radical scavenging agent. Irradiation only consumes small amounts of HT; its presence in polymeric hydrogels can significantly impact biomedical applications by its anti-oxidant and anti-microbial activities.


2004 ◽  
Vol 16 (3) ◽  
pp. 160-168 ◽  
Author(s):  
A. Ravi Kumar ◽  
Parameswara Achutha Kurup

Background/aims:The isoprenoid pathway produces three key metabolites: endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins) and ubiquinone (free radical scavenger). The role of the isoprenoid pathway in the pathogenesis of sarcoidosis in relation to hemispheric dominance was studied.Methods:The isoprenoid pathway-related cascade was assessed in patients with systemic sarcoidosis with pulmonary involvement. The pathway was also assessed in patients with right hemispheric, left hemispheric and bihemispheric dominance for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis.Results:In patients with sarcoidosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in the cholesterol:phospholipid ratio and a reduction in the glycoconjugate level of red blood cell (RBC) membrane in this group of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. In individuals with left hemispheric dominance the patterns were reversed.Conclusions:Endogenous digoxin, by activating the calcineurin signal transduction pathway of T cells, can contribute to immune activation in sarcoidosis. An altered glycoconjugate metabolism can lead to the generation of endogenous self-glycoprotein antigens in the lung as well as other tissues. Increased free radical generation can also lead to immune activation. The role of a dysfunctional isoprenoid pathway and endogenous digoxin in the pathogenesis of sarcoidosis in relation to right hemispheric chemical dominance is discussed. All the patients with sarcoidosis were right-handed/left hemispheric dominant according to the dichotic listening test, but their biochemical patterns were suggestive of right hemispheric chemical dominance. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test.


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