Autophagy in farm animals: current knowledge and future challenges

Tesseraud, Sophie; Avril, Pascale; Bonnet, Muriel; Bonnieu, Anne; Cassar-Malek, Isabelle; Chabi, Béatrice; Dessauge, Frédéric; Gabillard, Jean-Charles; Perruchot, Marie-Hélène; Seiliez, Iban

doi:10.1080/15548627.2020.1798064

Cited by 23 publications

(11 citation statements)

References 226 publications

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“…The AMPKα/mTOR signal pathway is the critical factor regulating autophagosome formation ( 29 , 30 ). Furthermore, mTOR is a serine/threonine protein kinase in the mTORC1 complex and a major regulator of autophagy ( 31 ). Activation of AMPK may cause autophagy by negatively modulating mTOR ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Prototheca bovis induces autophagy in bovine mammary epithelial cells via the HIF-1α and AMPKα/ULK1 pathway

Zhao

Xu²,

Barkema³

et al. 2022

Front. Immunol.

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Prototheca bovis, a highly contagious pathogen, causes bovine mastitis, resulting in premature culling of affected cows and severe economic losses. Infection with P. bovis caused oxidative stress and apoptosis in bovine mammary epithelial cells (bMECs); however, mechanisms underlying P. bovis-induced autophagy remain unclear. Therefore, the autophagy flux induced by P. bovis in bMECs was analyzed by Western blot and laser scanning confocal microscopy. Expression levels of proteins in the HIF-1α and AMPKα/ULK1 pathway, including HIF-1α, AMPKα, p-AMPKα, ULK1, p-ULK1, mTOR, and p-mTOR, plus expression of autophagy-related genes including SQSTM1/p62, Atg5, Beclin1, and LC3II/LC3I, were quantified with Western blot. Infection with P. bovis induced autophagosomes and LC3 puncta in bMECs that were detected using transmission electron microscopy and laser scanning confocal microscopy, respectively. In addition, lysosome-associated proteins Rab7 and LAMP2a, and lysosomal activity were measured with Western blot and laser scanning confocal microscopy. Infection with P. bovis induced an unobstructed autophagic flux, increased protein expression of LC3II/LC3I, and decreased SQSTM1/p62 protein expression at 6 hpi. Furthermore, P. bovis upregulated protein expression in the HIF-1α and AMPKα/ULK1 pathway and increased the ratio of LC3II/LC3I, implying autophagy was activated in bMECs. However, deletion of AMPKα or ULK1 decreased LC3II/LC3I expression levels and LC3 puncta numbers, suggesting that autophagy was inhibited in bMECs. Additionally, deficiency of HIF-1α decreased protein expression of AMPKα and ULK1 as well as LC3 puncta numbers, and autophagy induced by P. bovis was also inhibited in bMECs. At 6 hpi, lysosome-associated protein Rab7 was decreased and LAMP2a was increased, indicating normal autophagy. In contrast, at 12 hpi, expression of Rab7 and LAMP2a proteins indicated that autophagy was inhibited in bMECs at that time. Therefore, we confirmed that P. bovis infection induced autophagy in bMECs via the HIF-1α and AMPKα/ULK1 pathway, with involvement of lysosome-associated protein Rab7 and LAMP2a.

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Section: Discussionmentioning

confidence: 99%

Prototheca bovis induces autophagy in bovine mammary epithelial cells via the HIF-1α and AMPKα/ULK1 pathway

Zhao

Xu²,

Barkema³

et al. 2022

Front. Immunol.

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“…LPS induced cardiomyocyte autophagy through miR-590-3p/AMPK/mTOR signaling pathway [ 49 ]. Recent studies have also found that autophagy plays an important role in the development of ruminant diseases [ 50 ]. However, whether autophagy is involved in renal injury in bovine during transport stress remains unclear.…”

Section: Discussionmentioning

confidence: 99%

The combination of high glucose and LPS induces autophagy in bovine kidney epithelial cells via the Notch3/mTOR signaling pathway

Cui

Guo

Zhang³

et al. 2022

BMC Vet Res

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Background Aside respiratory diseases, beef cattle may also suffer from serious kidney diseases after transportation. Hyperglycemia and gram-negative bacterial infection may be the main reasons why bovine is prone to severe kidney disease during transportation stress, however, the precise mechanism is still unclear. The purpose of the current study is to explore whether the combined treatment of high glucose (HG) and lipopolysaccharide (LPS) could induce madin-darby bovine kidney (MDBK) cells injury and autophagy, as well as investigate the potential molecular mechanisms involved. Results As we discovered, the combined effect of HG and LPS decreased MDBK cells viability. And, HG and LPS combination also induced autophagy in MDBK cells, which was characterized by increasing the expression of LC3-II/I and Beclin1 and decreasing p62 expression. LC3 fluorescence signal formation was also significantly increased by HG and LPS combination treatment. Furthermore, we measured whether the mammalian target of rapamycin (mTOR) and the Notch3 signaling pathways were involved in HG and LPS-induced autophagy. The results showed that the combination of HG and LPS significantly increased the protein expression of Notch3 and decreased protein expression of p-mTOR, indicating that Notch3 and mTOR signaling pathways were activated. However, co-treatment with the Notch3 inhibitor (DAPT) could reverse the induction of autophagy, and increased the protein expression of p-mTOR. Conclusions This study demonstrated that the combination effect of HG and LPS could induce autophagy in MDBK cells, and the Notch3/mTOR signaling pathway was involved in HG and LPS-induced autophagy.

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“…Under those conditions, insulin sensitivity is dramatically reduced ( Fang et al, 2022 ) and, as a whole, these events confirm the original observations in model organisms linking ER stress and immunometabolism ( Mathis and Shoelson, 2011 ). An ancillary process recently recognized as central for the control of ER stress and its cascade of negative events in cells is autophagy, i.e., the transport of cellular components to the lysosome for degradation ( Tesseraud et al, 2021 ). Metabolic stressors such as fatty acids, similar to their effect on ER function, inhibit autophagy and lead to inflammation and oxidative stress in tissues, with the activity of NFE2L2 being central for enhancing autophagy and reducing these negative effects ( Shen et al, 2021 ; Chang et al, 2022 ).…”

Section: The Er and Its Physiological Role In Metabolic Organsmentioning

confidence: 99%

Immunometabolism in livestock: triggers and physiological role of transcription regulators, nutrients, and microbiota

Loor

Elolimy

2022

Animal Frontiers

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Autophagy in farm animals: current knowledge and future challenges

Cited by 23 publications

References 226 publications

Prototheca bovis induces autophagy in bovine mammary epithelial cells via the HIF-1α and AMPKα/ULK1 pathway

Prototheca bovis induces autophagy in bovine mammary epithelial cells via the HIF-1α and AMPKα/ULK1 pathway

The combination of high glucose and LPS induces autophagy in bovine kidney epithelial cells via the Notch3/mTOR signaling pathway

Immunometabolism in livestock: triggers and physiological role of transcription regulators, nutrients, and microbiota

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