Leucine mediates autophagosome-lysosome fusion and improves sperm motility by activating the PI3K/Akt pathway

Zhang, Jin; Zhang, Xuemei; Liu, Yingjie; 蘇, 智慧; Dawar, Farman Ullah; Hong, Daojun; He, Yan; Gui, Jian‐Fang; Mei, Jie

doi:10.18632/oncotarget.22910

Cited by 38 publications

(30 citation statements)

References 41 publications

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“…Leucine concentration in SP was found to be positively correlated with the percentage of viable sperm with a non-intact acrosome (P = 0.038) and negatively associated with the loss of total (P = 0.039) and progressive (P = 0.024) motility after 72 h of liquid storage. Despite the fact that no information regarding leucine effect on sperm performance is available in mammals, the addition of this metabolite is known to have a positive effect on the motility of zebrafish sperm (Zhang et al, 2017). Similarly, our findings revealed that hypotaurine concentration in SP was negatively related with higher loss of progressive motility (P = 0.018) after liquid storage at 17 • C. In this context, it is worth mentioning that hypotaurine supplementation has been reported to exert a positive impact upon sperm motility in mammalian species, such as hamsters (Boatman et al, 1990) or humans (Holmes et al, 1992;Brugnon et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Metabolite Profiling of Pig Seminal Plasma Identifies Potential Biomarkers for Sperm Resilience to Liquid Preservation

Mateo‐Otero

Fernández-López

Ribas-Maynou

et al. 2021

Front. Cell Dev. Biol.

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Metabolomic approaches allow the study of downstream gene expression events since metabolites are considered as the products of cell signaling pathways. For this reason, many studies in humans have already been conducted to determine the influence of the metabolites present in seminal plasma (SP) on sperm physiology, and to identify putative biomarkers. However, in livestock species, these relationships are yet to be uncovered. Thus, the present study aimed to explore: (i) if concentrations of metabolites in pig SP are related to sperm quality and functionality, and (ii) if they could predict the sperm resilience to liquid storage at 17°C. To this end, 28 ejaculates were individually collected and split into three aliquots: one was used for SP analysis through nuclear magnetic resonance (NMR) spectroscopy; another served for the evaluation of sperm concentration and morphology; and the last one was utilized to determine sperm functionality parameters using computer-assisted sperm analysis (CASA) and flow cytometry after 0 h and 72 h of liquid-storage at 17°C. NMR analysis allowed the identification and quantification of 23 metabolites present in pig SP which, except for fumarate, were not observed to follow a breed-dependent behavior. Moreover, specific relationships between metabolites and sperm variables were identified: (i) glutamate, methanol, trimethylamine N-oxide, carnitine, and isoleucine were seen to be related to some sperm quality and functionality parameters evaluated immediately after semen collection; (ii) leucine, hypotaurine, carnitine and isoleucine were found to be associated to the sperm ability to withstand liquid storage; and (iii) Bayesian multiple regression models allowed the identification of metabolite patterns for specific sperm parameters at both 0 h and 72 h. The identification of these relationships opens up the possibility of further investigating these metabolites as potential sperm functional biomarkers.

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Section: Discussionmentioning

confidence: 99%

Metabolite Profiling of Pig Seminal Plasma Identifies Potential Biomarkers for Sperm Resilience to Liquid Preservation

Mateo‐Otero

Fernández-López

Ribas-Maynou

et al. 2021

Front. Cell Dev. Biol.

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“…Chloroquine inhibits the process of degradation of the autophagosome-lysosome, blocking the normal process of autophagy. This inhibition leads to the accumulation of LC3 within the cell and inhibits the degradation of P62, which down-regulates the autophagy level [35,36]. Under the electron microscope, we observed that chloroquine inhibits the process of degradation of macrophage autophagosome-lysosome and decreases the expression of LC3 and Beclin-1 and increaseds the expression of P62.…”

Section: Discussionmentioning

confidence: 99%

Effects of autophagy on macrophage adhesion and migration in diabetic nephropathy

et al. 2019

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Objective: Macrophage infiltration in kidney is a major pathological feature of diabetic nephropathy (DN), which has been demonstrated associate with macrophages autophagy homeostasis. However, the relationships between autophagy and the infiltration response related of macrophages adhesion and migration are unknown. This study aims to investigate the impact of macrophages adhesion and migration by modulating autophagy. Methods: In vivo, rats were randomly distributed into control (NC) and DN groups. The pathological changes in renal tissue were assessed, and expression of CD68, LC3, P62 were analyzed. In vitro, RAW264.7 cells were divided into NC and high glucose (HG) groups. The capacity of macrophages adhesion migration and the expression of autophagy markers were observed with and without autophagy modulators (rapamycin, 3-methyladenine, chloroquine, and bafilomycin A1 for RAPA, 3-MA, CQ, BAFA). The macrophages autophagosome and the process of degradation and fusion of autophagosome-lysosome were observed by electron microscopy. Results: In vivo, renal injury is aggravated in diabetic rat compared with NC group. The autophagy level is inhibited in renal tissues of DN group with the increasing expression of CD68 and P62, while expression level of LC3 decreased ( p < .05). In vitro, HG and 3-MA reduce the numbers of autophagosome of macrophages to inhibit autophagy level with decrease expression of LC3 and Beclin-1, but increase expression of P62, which promote the adhesion and migration capacity of macrophages ( p < .05). Moreover, CQ and BAFA suppress autophagy level by inhibiting the process of autophagosome-lysosome degradation and fusion of macrophages, as well as the expression of LC3 and Beclin-1. We notice an increase expression of P62 by CQ and BAFA stimulation ( p < .05). CQ and BAFA further facilitate the adhesion and migration capacity of macrophages. However, RAPA increases the numbers of macrophages autophagosome that inhibited by HG, resulting in a recovery of autophagy level with increase expression of LC3 and Beclin-1, whereas a reduction expression of P62, which lead to inhibition of adhesion and migration of macrophages induced by HG ( p < .05) Conclusions: High glucose efficiently reduced the level of macrophage autophagy, following macrophages adhesion and migration enhanced when autophagy is suppressed. Activation of autophagosome improve the level of autophagy, but leading to a reduction of the macrophages adhesion and migration. While, inhibiting the process of degradation and fusion of autophagosome-lysosome suppress the level of autophagy and promote the macrophages adhesion and migration. These results indicate that high glucose may play an important role in macrophages adhesion and migration through modulating autophagy activities in diabetic nephropathy.

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“…Isolated RNA was reverse transcribed into cDNA was by Prime Script TM RT reagent Kit with gDNA Eraser (Stratagene, Takara). Real-time PCR was performed on ABI-7500 real-time PCR machine (Applied Biosystems, USA) and β-actin was used to normalize the expression values(67). The primer sequences used in qRT-PCR are listed in tables 1, 2, and 3.…”

Section: Methodsmentioning

confidence: 99%

Autophagy-related genesatg7andbeclin1are essential for energy metabolism and survival during the larval-to-juvenile transition stage of zebrafish

Mawed

Zhang

Ren

et al. 2019

Preprint

Self Cite

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High mortality is usually observed during the transition from larvae to juvenile in teleost which is related to the transition from endogenous to exogenous feeding. Autophagy is an evolutionary regulated cellular mechanism highly conserved in eukaryotic organisms to maintain energy homeostasis against stress including starvation. To investigate whether autophagy plays a role during the larval-juvenile transition, we generated atg7 and beclin1 zebrafish mutant lines using CRISPR/Cas9 technology. In this study, both atg7 and beclin1 null zebrafish exhibited a normal body confirmation; nevertheless, they completely died around 15 dpf and 9 dpf respectively. During larval-juvenile transition period, atg7 and beclin1 mutants were unable to cope with the metabolic stress after yolk absorption at 5 dpf and fail to activate autophagy in response to nutrient restriction, and without external feeding, all mutants died nearly at 8 dpf. Dramatic defects in the intestine architecture and metabolic functions in the liver were observed even though providing larvae with an external food supply, suggesting that autophagy isn’t only important during yolk depletion but also within food plenty. Treatment with rapamycin, an activator of autophagy, could effectively extend the survival time of both atg7 and beclin1 null zebrafish through lowering the metabolic rate while it couldn’t activate autophagy in mutants via the canonical pathway. Our findings provided a molecular evidence for the physiological, histological and metabolic changes that occur during the transition process from the larval to the juvenile stages and the chief role of autophagy on the body metabolism during these turning milestones.Author summaryZebrafish Danio rerio has emergrd one of the most powerful research models for studying genes expression during early embryogenesis and postnatal development. On the basis of the cell mechanisms, Macroautphagy, a natural regulated pathway disassembles unnecessary or dysfunctional components orchestrated by more than 36 autophagy related-genes conserved from yeast to mammals. Among those genes are atg7 and beclin1 which have been proved to play an important role in regulating post natal development in some mammals however their roles during zebrafish development still unedited. During this research, CRISPER/CAS9 were adopted to know atg7 and beclin1 knockout effects on the mutants’ metabolism during shifting from maternal yolk acquisition to exogenous feeding and the role of autophagy during the larvae to pre-juvenile development. Herein, we found out that larvae couldn’t abandon autophagy in both fasting and feeding conditions as larvae died earlier before pre-juvenile development despite feeding declaring the importance of autophagy not only to provide the cell with essential nutrients during starvation but also to get rid of cargos inside the eukaryotic cells. Briefly, if the larvae didn’t recycle those cargos due to autophagy perturbations, they will die despite providing suitable conditions including food and acclimatization.

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Leucine mediates autophagosome-lysosome fusion and improves sperm motility by activating the PI3K/Akt pathway

Cited by 38 publications

References 41 publications

Metabolite Profiling of Pig Seminal Plasma Identifies Potential Biomarkers for Sperm Resilience to Liquid Preservation

Metabolite Profiling of Pig Seminal Plasma Identifies Potential Biomarkers for Sperm Resilience to Liquid Preservation

Effects of autophagy on macrophage adhesion and migration in diabetic nephropathy

Autophagy-related genesatg7andbeclin1are essential for energy metabolism and survival during the larval-to-juvenile transition stage of zebrafish

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