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miR-98 and its host gene Huwe1 target Caspase-3 in Silica nanoparticles-treated male germ cells

Journal Article · · Scientific Reports
DOI:https://doi.org/10.1038/srep12938· OSTI ID:1624787
 [1];  [2];  [3];  [2];  [2];  [2];  [4];  [5];  [6];  [7];  [2]
  1. Institute of Toxicology, Nanjing Medical University, Nanjing (China). State Key Laboratory of Reproductive Medicine; Nanjing Medical University, Nanjing (China). Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Jiangyin (China). School of Public Health; Department of Endocrinology, The Affiliated Jiangyin Hospital of Wuxi Clinical School of Medicine; DOE/OSTI
  2. Institute of Toxicology, Nanjing Medical University, Nanjing (China). State Key Laboratory of Reproductive Medicine; Nanjing Medical University, Nanjing (China). Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health
  3. Institute of Toxicology, Nanjing Medical University, Nanjing (China). State Key Laboratory of Reproductive Medicine; Nanjing Medical University, Nanjing (China). Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health; Nanjing Medical University, Nanjing (China). Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Department of Cancer & DNA Damage Responses, Life Sciences Division
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States), The Molecular Foundry
  6. Nanjing Medical University, Jiangyin (China). Department of Endocrinology, The Affiliated Jiangyin Hospital of Wuxi Clinical School of Medicine
  7. Medical School, Southeast University, Nanjing, Jiangsu (China)
+ Show Author Affiliations

Silica nanoparticles (NP) is one of the most commonly used nanomaterials with potential health hazards. However, the effects of Silica NP on germ cells and the underlying mechanisms are still unclear. In this study, GC-2 and TM-4, which are two different types of male germ cells were exposed to Silica NP for 24h and then general cytotoxicity and multi-parameter cytotoxicity were evaluated. Our results showed that Silica NP could induce apoptosis in GC-2 cells. Transmission electron microscopy (TEM) results showed that Silica NP was localized in the lysosomes of GC-2 cells. High content screening (HCS) showed that Silica NP exposure could increased cell permeabilization and decreased mitochondrial membrane potential in GC-2 cells. The mRNA and protein levels of apoptosis markers (Bax, Caspase-3, Caspase-9) in GC-2 cells were significantly increased, while Bcl-2 was decreased. Accordingly, the expression level of miR-98, which can regulate Caspase-3, was significantly decreased. Huwe1, the host gene of miR-98, was positively associated with miR-98 expression after Silica NP exposure. Dual luciferase reporter assay suggested that miR-98 directly targets Caspase-3. These results suggest that Silica NP induces apoptosis via loss of mitochondrial membrane potential and Caspase-3 activation, while miR-98 plays key role in modulating this effect.

Sponsoring Organization:
USDOE
DOE Contract Number:
AC02-05CH11231
OSTI ID:
1624787
Journal Information:
Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 5; ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English

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