Next Article in Journal
Fibroinflammatory Signatures Increase with Age in the Human Ovary and Follicular Fluid
Next Article in Special Issue
Simulated Microgravity Remodels Extracellular Matrix of Osteocommitted Mesenchymal Stromal Cells
Previous Article in Journal
Magnetic Particles with Polymeric Shells Bearing Cholesterol Moieties Sensitize Breast Cancer Cells to Low Doses of Doxorubicin
Previous Article in Special Issue
The Effect of Space Travel on Bone Metabolism: Considerations on Today’s Major Challenges and Advances in Pharmacology
Article

Hypergravity Load Modulates Acetaminophen Nephrotoxicity via Endoplasmic Reticulum Stress in Association with Hepatic microRNA-122 Expression

1
College of Pharmacy, Seoul National University, Seoul 08826, Korea
2
Aerospace Medical Center, ROKAF, Cheong-ju 360-842, Korea
3
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang-si, Gyeonggi-Do 10326, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Daniela Grimm
Int. J. Mol. Sci. 2021, 22(9), 4901; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094901
Received: 26 April 2021 / Revised: 3 May 2021 / Accepted: 3 May 2021 / Published: 5 May 2021
(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)
Hypergravity conditions may subject the kidney to intrinsic stress and lead to hemodynamic kidney dysfunction. However, the mechanisms underlying this phenomenon remain unclear. Accumulation of unfolded proteins in the endoplasmic reticulum (i.e., ER stress) is often observed in kidney diseases. Therefore, this study investigated whether hypergravity stress alters acetaminophen-induced renal toxicity in vivo, as well as the molecular mechanisms involved in this process. C57BL/6 mice were submitted to one or three loads of +9 Gx hypergravity for 1 h with or without acetaminophen (APAP) treatment. The protein levels of cell survival markers, including pAKT and pCREB, were decreased in the kidney after acetaminophen treatment with a single hypergravity load. Additionally, the combined treatment increased kidney injury markers, serum creatinine, and Bax, Bcl2, and Kim-1 transcript levels and enhanced ER stress-related markers were further. Moreover, multiple hypergravity loads enabled mice to overcome kidney injury, as indicated by decreases in serum creatinine content and ER stress marker levels, along with increased cell viability indices. Similarly, multiple hypergravity loads plus APAP elevated miR-122 levels in the kidney, which likely originated from the liver, as the levels of primary miR-122 increased only in the liver and not the kidney. Importantly, this phenomenon may contribute to overcoming hypergravity-induced kidney injury. Taken together, our results demonstrate that APAP-exposed mice submitted to a single load of hypergravity exhibited more pronounced kidney dysfunction due to increased ER stress, which may be overcome by repetitive hypergravity loads presumably due to increased production of miR-122 in the liver. Thus, our study provides novel insights into the mechanisms by which hypergravity stress plus APAP medication induce kidney injury, which may be overcome by repeated hypergravity exposure. View Full-Text
Keywords: hypergravity; ER stress; kidney injury; miR-122; adaptation hypergravity; ER stress; kidney injury; miR-122; adaptation
Show Figures

Figure 1

MDPI and ACS Style

Wu, H.-M.; Lee, S.-G.; Oh, C.-S.; Kim, S.-G. Hypergravity Load Modulates Acetaminophen Nephrotoxicity via Endoplasmic Reticulum Stress in Association with Hepatic microRNA-122 Expression. Int. J. Mol. Sci. 2021, 22, 4901. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094901

AMA Style

Wu H-M, Lee S-G, Oh C-S, Kim S-G. Hypergravity Load Modulates Acetaminophen Nephrotoxicity via Endoplasmic Reticulum Stress in Association with Hepatic microRNA-122 Expression. International Journal of Molecular Sciences. 2021; 22(9):4901. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094901

Chicago/Turabian Style

Wu, Hong-Min, Sang-Gil Lee, Choong-Sik Oh, and Sang-Geon Kim. 2021. "Hypergravity Load Modulates Acetaminophen Nephrotoxicity via Endoplasmic Reticulum Stress in Association with Hepatic microRNA-122 Expression" International Journal of Molecular Sciences 22, no. 9: 4901. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094901

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop