BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells
Accumulation of silica nanoparticles (SNPs) in the testes leads to male reproductive toxicity. However, little is known about the effect and mechanistic insights of SNP-induced autophagy on apoptosis in Leydig cells. In this study, we aimed to verify the role of SNP-induced autophagy in apoptosis an...
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MDPI AG
2022-06-01
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| author | Qianru Zhang Jason William Grunberger Nitish Khurana Xin Zhou Xianyu Xu Hamidreza Ghandehari Fenglei Chen |
| author_facet | Qianru Zhang Jason William Grunberger Nitish Khurana Xin Zhou Xianyu Xu Hamidreza Ghandehari Fenglei Chen |
| author_sort | Qianru Zhang |
| collection | DOAJ |
| description | Accumulation of silica nanoparticles (SNPs) in the testes leads to male reproductive toxicity. However, little is known about the effect and mechanistic insights of SNP-induced autophagy on apoptosis in Leydig cells. In this study, we aimed to verify the role of SNP-induced autophagy in apoptosis and explore the possible underlying mechanism in mouse primary Leydig cells (PLCs). H&E staining showed that SNPs changed the histological structures of the testes, including a reduction in the Leydig cell populations in vivo. CCK-8 assay showed that SNPs decreased cell viability, and flow cytometry showed that SNPs increased cell apoptosis, both in a dose-dependent manner in vitro. Additionally, Western blotting further found that SNPs activated autophagy by an increase in BECLIN-1, ATG16L, and LC3-II levels and promoted the intrinsic pathway of apoptosis by an increase in the BAX/BCL-2 ratio, cleaved the caspase 8 and caspase 3 levels. Furthermore, autophagy decreased SNP-induced apoptosis via regulation of the caspase 8 level combined with rapamycin, 3-methyladenine, and chloroquine. BECLIN-1 depletion increased the caspase 8 level, leading to an increase in SNP-induced cell apoptosis. Collectively, this evidence demonstrates that SNPs activated BECLIN-1-mediated autophagy, which prevented SNP-induced testicular toxicity via the inhibition of caspase 8-mediated cell apoptosis in Leydig cells. |
| first_indexed | 2024-03-10T00:09:45Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:09:45Z |
| publishDate | 2022-06-01 |
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| spelling | doaj.art-0a01e427a17545b883c8fd3b92d33ad62023-11-23T16:00:33ZengMDPI AGCells2073-44092022-06-011112186310.3390/cells11121863BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig CellsQianru Zhang0Jason William Grunberger1Nitish Khurana2Xin Zhou3Xianyu Xu4Hamidreza Ghandehari5Fenglei Chen6Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaDepartment of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112-5001, USADepartment of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112-5001, USAInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaDepartment of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112-5001, USAInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaAccumulation of silica nanoparticles (SNPs) in the testes leads to male reproductive toxicity. However, little is known about the effect and mechanistic insights of SNP-induced autophagy on apoptosis in Leydig cells. In this study, we aimed to verify the role of SNP-induced autophagy in apoptosis and explore the possible underlying mechanism in mouse primary Leydig cells (PLCs). H&E staining showed that SNPs changed the histological structures of the testes, including a reduction in the Leydig cell populations in vivo. CCK-8 assay showed that SNPs decreased cell viability, and flow cytometry showed that SNPs increased cell apoptosis, both in a dose-dependent manner in vitro. Additionally, Western blotting further found that SNPs activated autophagy by an increase in BECLIN-1, ATG16L, and LC3-II levels and promoted the intrinsic pathway of apoptosis by an increase in the BAX/BCL-2 ratio, cleaved the caspase 8 and caspase 3 levels. Furthermore, autophagy decreased SNP-induced apoptosis via regulation of the caspase 8 level combined with rapamycin, 3-methyladenine, and chloroquine. BECLIN-1 depletion increased the caspase 8 level, leading to an increase in SNP-induced cell apoptosis. Collectively, this evidence demonstrates that SNPs activated BECLIN-1-mediated autophagy, which prevented SNP-induced testicular toxicity via the inhibition of caspase 8-mediated cell apoptosis in Leydig cells.https://www.mdpi.com/2073-4409/11/12/1863silica nanoparticlesBECLIN-1autophagyapoptosisLeydig cellstesticular toxicity |
| spellingShingle | Qianru Zhang Jason William Grunberger Nitish Khurana Xin Zhou Xianyu Xu Hamidreza Ghandehari Fenglei Chen BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells Cells silica nanoparticles BECLIN-1 autophagy apoptosis Leydig cells testicular toxicity |
| title | BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells |
| title_full | BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells |
| title_fullStr | BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells |
| title_full_unstemmed | BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells |
| title_short | BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells |
| title_sort | beclin 1 mediated autophagy suppresses silica nanoparticle induced testicular toxicity via the inhibition of caspase 8 mediated cell apoptosis in leydig cells |
| topic | silica nanoparticles BECLIN-1 autophagy apoptosis Leydig cells testicular toxicity |
| url | https://www.mdpi.com/2073-4409/11/12/1863 |
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