Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy

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Abstract

Background

Probiotic supplementation has been shown to be beneficial and is now widely promoted as an auxiliary medicine for maternal health, but the underlying mechanism is still unclear. Thus, this study aimed to explore the effects of probiotic supplementation on the placental autophagy-related proteins LC3 and Beclin1.

Method

A population-based cohort of specimens was collected under sterile conditions from 37 healthy nulliparous pregnant women who underwent systemic examination and delivered at the First Affiliated Hospital of Jinan University (Guangzhou, China). At 32 weeks of gestation, the pregnant women in the probiotic group were orally supplemented with golden bifid, and the pregnant women in the control group received no probiotic. Pregnant women with pregnancy-associated complications were excluded in the follow-up period, and 25 pregnant women undergoing spontaneous delivery were enrolled. The placental tissue specimens were collected at term. Western blotting was used to detect the protein expression, and qRT-PCR was used to detect the mRNA expression of the placental autophagy-related proteins LC3 and Beclin1.

Results

①There was no significant difference in the expression levels of either LC3 or Beclin1 protein between the two groups ( P > 0.05). ②Probiotic supplementation induced a modest but not significant decrease in the content of LC3-mRNA with a significant decrease in the content of Beclin1-mRNA ( P < 0.05).

Conclusion

Our study indicates that probiotic supplementation may reduce Beclin1-mRNA levels.

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Most cited references 17

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Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells.

T Kanzawa, I Germano, T Komata … (2004)

Autophagy is originally named as a process of protein recycling. It begins with sequestering cytoplasmic organelles in a membrane vacuole called autophagosome. Autophagosomes then fuse with lysosomes, where the materials inside are degraded and recycled. To date, however, little is known about the role of autophagy in cancer therapy. In this study, we present that temozolomide (TMZ), a new alkylating agent, inhibited the viability of malignant glioma cells in a dose-dependent manner and induced G2/M arrest. At a clinically achievable dose (100 microM), TMZ induced autophagy, but not apoptosis in malignant glioma cells. After the treatment with TMZ, microtubule-associated protein light-chain 3 (LC3), a mammalian homologue of Apg8p/Aut7p essential for amino-acid starvation-induced autophagy in yeast, was recruited on autophagosome membranes. When autophagy was prevented at an early stage by 3-methyladenine, a phosphatidylinositol 3-phosphate kinase inhibitor, not only the characteristic pattern of LC3 localization, but also the antitumor effect of TMZ was suppressed. On the other hand, bafilomycin A1, a specific inhibitor of vacuolar type H(+)-ATPase, that prevents autophagy at a late stage by inhibiting fusion between autophagosomes and lysosomes, sensitized tumor cells to TMZ by inducing apoptosis through activation of caspase-3 with mitochondrial and lysosomal membrane permeabilization, while LC3 localization pattern stayed the same. These results indicate that TMZ induces autophagy in malignant glioma cells. Application of an autophagy inhibitor that works after the association of LC3 with autophagosome membrane, such as bafilomycin A1, is expected to enhance the cytotoxicity of TMZ for malignant gliomas.

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Autophagy-related proteins, LC3 and Beclin-1, in placentas from pregnancies complicated by preeclampsia.

Hoan-Suk Choi, Soo Oh, Jung Kim … (2008)

The objective of this study is to investigate the expression of autophagy-related proteins (LC3 and beclin-1) in human placentas and the changes they undergo in the placentas from pregnancies complicated by preeclampsia (PE) and to explore the regulatory mechanisms of these proteins in JEG-3 cells in response to hypoxia or cytokine treatment.The presence of autophagosomes was confirmed with electron microscopy and the expression of LC3 and beclin-1 by immunoimaging methods in human placental trophoblasts. Compared with the placentas from normal pregnancies, the expression of LC3-II protein, but not beclin-1, was increased in the placentas from severe PE. In JEG-3 cells, hypoxia (O(2) < 1%) induced a modest but not significant increase in the expression of LC3-II with a significant decrease in the expression of beclin-1. Meanwhile, TNF-alpha treatment induced a significant increase in the expression of LC3-II without a significant change in the expression of beclin-1. Our data suggests that increased autophagic activity in the placenta may be implicated in the pathophysiology of PE.

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Autophagy and adaptive immunity.

Victoria L. Crotzer, Janice Blum (2010)

Autophagy plays an important role in maintaining intracellular homeostasis by promoting the transit of cytoplasmic material, such as proteins, organelles and pathogens, for degradation within acidic organelles. Yet, in immune cells, autophagy pathways serve an additional role in facilitating intracellular surveillance for pathogens and changes in self. Autophagy pathways can modulate key steps in the development of innate and adaptive immunity. In terms of adaptive immunity, autophagy regulates the development and survival of lymphocytes as well as the modulation of antigen processing and presentation. Specialized forms of autophagy may be induced by some viral pathogens, providing a novel route for major histocompatibility complex (MHC) class I antigen presentation and enhanced CD8(+) T-cell responses. Autophagy induction in target cells also increases their potential to serve as immunogens for dendritic cell cross-presentation to CD8(+) T cells. The requirement for autophagy in MHC class II presentation of cytoplasmic and nuclear antigens is well established, yet recent studies also point to a critical role for autophagy in modulating CD4(+) T-cell responses to phagocytosed pathogens. Autophagy pathways can also modulate the selection and survival of some CD4(+) T cells in the thymus. However, much still remains to be learned mechanistically with respect to how autophagy and autophagy-linked genes regulate pathogen recognition and antigen presentation, as well as the development and survival of immune cells.

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Author and article information

Contributors

Xiaomin Xiao: Xiaoxiaomin55@yeah.net

Journal

Journal ID (nlm-ta): BMC Pregnancy Childbirth

Journal ID (iso-abbrev): BMC Pregnancy Childbirth

Title: BMC Pregnancy and Childbirth

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2393

Publication date (Electronic): 15 April 2020

Publication date PMC-release: 15 April 2020

Publication date Collection: 2020

Volume: 20

Electronic Location Identifier: 216

Affiliations

[1 ]GRID grid.412601.0, ISNI 0000 0004 1760 3828, Department of Obstetrics and Gynecology, , The First Affiliated Hospital of Jinan University, ; Guangzhou, China

[2 ]GRID grid.412558.f, ISNI 0000 0004 1762 1794, Department of Obstetrics and Gynecology, , The Third Affiliated Hospital of Sun Yat-Sen University, ; Guangzhou, China

[3 ]Department of Otolaryngology, Shenzhen Long Hua District Central Hospital, Shenzhen, China

[4 ]GRID grid.258164.c, ISNI 0000 0004 1790 3548, Faculty of Medicine, International School, , Jinan University, ; Guangzhou, China

Article

Publisher ID: 2905

DOI: 10.1186/s12884-020-02905-z

PMC ID: 7161261

PubMed ID: 32295534

SO-VID: e9530a98-5829-472b-882c-d6d26d2e89ef

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 6 December 2019

Date accepted : 27 March 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 21317237

Award Recipient : Xiaomin Xiao

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ScienceOpen disciplines: Obstetrics & Gynecology

Keywords: probiotic,autophagy,normal pregnancy,spontaneous delivery

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ScienceOpen disciplines: Obstetrics & Gynecology

Keywords: probiotic, autophagy, normal pregnancy, spontaneous delivery

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Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy

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Abstract

Background

Method

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Conclusion

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Most cited references 17

Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells.

Autophagy-related proteins, LC3 and Beclin-1, in placentas from pregnancies complicated by preeclampsia.

Autophagy and adaptive immunity.

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Cited by 7

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