Skip to main content
SpringerLink
Log in

Stimulated Microgravity Affects Mitochondrial Homeostasis in the Harderian Glands of Mice

  • Experimental Papers
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

Long-term exposure to microgravity can cause alterations in the structure and function of the eyes, including the Harderian glands (HG) which are situated at the posterior part of the orbit in proximity to the eyeball. Whether microgravity will affect the morphology and function of HG and its mitochondrial homeostasis is not clear. In the present study, we investigated how tail suspension (TS) for 2 and 4 weeks (TS2 and TS4) affects mitochondrial ultrastructure and the underlying mechanisms involved in apoptosis, mitochondrial fission, autophagy, and fusion-related signaling in the HG. The results showed that after 2 weeks of TS treatment, the number of mitochondria in the HG of mice increased; however, the number of mitochondria in the TS4 group significantly decreased when compared to the TS2 group (p < 0.05). In the TS2 group, the rate of Parkin phosphorylation and the protein expression levels of OPA1, MFN1, and MFN2 were all found to be decreased. However, in the TS4 group, the rate of Parkin phosphorylation and the protein expression levels of OPA1 were increased compared with the TS2 group. In both TS groups, slight nuclear deformation and increased caspase-3 activity were observed. In general, the augmented quantity of mitochondria observed in the TS2 group may be attributed to reduced levels of mitochondrial autophagy and fusion. After 4 weeks of TS, the number of mitochondria decreased, which was attributed to an increase in the levels of mitochondrial autophagy and fusion. These findings indicate that mitochondria of HGs exhibit an adaptive response to the simulated microgravity environment, resulting in remodeling that enhances the completeness of mitochondrial morphology and structure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.

REFERENCES

  1. Yoon N, Na K, Kim HS (2017) Simulated weightlessness affects the expression and activity of neuronal nitric oxide synthase in the rat brain. Oncotarget 8: 30692. https://doi.org/10.18632/oncotarget.15407

    Article  PubMed  PubMed Central  Google Scholar 

  2. Huang W, Chen C, Liu X (2018) Hindlimb suspensioninduced cell apoptosis in the posterior parietal cortex and lateral geniculate nucleus: corresponding changes in cFos protein and the PI3K/Akt signaling pathway. Acta Neurobiol Exp (Wars) 78: 220. https://doi.org/10.21307/ane-2018-020

  3. Mao XW, Nishiyama NC, Byrum SD, Stanbouly S, et al. (2019) Characterization of mouse ocular response to a 35-day spaceflight mission: Evidence of blood-retinal barrier disruption and ocular adaptations. Scientific Reports 9:8215. https://doi.org/10.1038/s41598-019-44696-0

  4. Oleynik EA, Naumova YS, Grigorieva YS, Bakhteeva VT, et al. (2022) Neurogenesis in the Hippocampus of Mice Exposed to Short-Term Hindlimb Unloading. Journal of Evolutionary Biochemistry and Physiology 58: 1119. https://doi.org/10.1134/s0022093022040159

  5. Chen HL, Qu LN, Li QD, Bi L, et al. (2009) Simulated microgravity-induced oxidative stress in different areas of rat brain. Acta Physiologica Sinica 61: 108.

  6. Zhang R, Ran HH, Cai LL, Zhu L, et al. (2014) Simulated microgravity-induced mitochondrial dysfunction in rat cerebral arteries. Faseb j 28: 2715. https://doi.org/10.1096/fj.13-245654

  7. Pompeiano O, D’ascanio P, Balaban E, Centini C, et al. (2004) Gene expression in autonomic areas of the medulla and the central nucleus of the amygdala in rats during and after space flight. Neuroscience 124: 53. https://doi.org/10.1016/j.neuroscience.2003.09.027

  8. Kharlamova A, Proshchina A, Gulimova V, Krivova Y, et al. (2021) Cerebellar morphology and behavioural correlations of the vestibular function alterations in weightlessness. Neuroscience and Biobehavioral Reviews 126: 314. https://doi.org/10.1016/j.neubiorev.2021.03.011

  9. Mikheeva I, Mikhailova G, Shtanchaev R, Arkhipov V, et al. (2021) Influence of a 30-day spaceflight on the structure of motoneurons of the trochlear nerve nucleus in mice. Brain Research 1758: 147331. https://doi.org/10.1016/j.brainres.2021.147331

  10. Wu NN, Zhang Y, Ren J (2019) Mitophagy, Mitochondrial Dynamics, and Homeostasis in Cardiovascular Aging. Oxid Med Cell Longev 2019: 9825061. https://doi.org/10.1155/2019/9825061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tilokani L, Nagashima S, Paupe V, Prudent J (2018) Mitochondrial dynamics: overview of molecular mechanisms. Essays Biochem 62: 341. https://doi.org/10.1042/EBC20170104

    Article  PubMed  PubMed Central  Google Scholar 

  12. Xie LL, Shi F, Tan Z, Li Y, et al. (2018) Mitochondrial network structure homeostasis and cell death. Cancer Sci 109: 3686. https://doi.org/10.1111/cas.13830

  13. Derkach KV, Bakhtyukov AA, Basova NE, Zorina Ii, et al. (2022) The Restorative Effect of Combined Insulin and C-Peptide Intranasal Administration on Hormonal Status and Hypothalamic Signaling in the Male Rat Model of Severe Short-Term Streptozotocin-Induced Diabetes. Journal of Evolutionary Biochemistry and Physiology 58: 677. https://doi.org/10.1134/s002209302203005x

  14. Meyer JN, Leuthner TC, Luz AL (2017) Mitochondrial fusion, fission, and mitochondrial toxicity. Toxicology 391: 42. https://doi.org/10.1016/j.tox.2017.07.019

    Article  CAS  PubMed  Google Scholar 

  15. Pickles S, Vigie P, Youle R J (2018) Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance. Curr Biol 28: R170. https://doi.org/10.1016/j.cub.2018.01.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bleicken S, Classen M, Padmavathi PV, Ishikawa T, et al. (2010) Molecular details of Bax activation, oligomerization, and membrane insertion. J Biol Chem 285: 6636. https://doi.org/10.1074/jbc.M109.081539

  17. Sakai T (1989) Major ocular glands (harderian gland and lacrimal gland) of the musk shrew (Suncus murinus) with a review on the comparative anatomy and histology of the mammalian lacrimal glands. J Morphol 201: 39. https://doi.org/10.1002/jmor.1052010105

    Article  CAS  PubMed  Google Scholar 

  18. Payne AP (1994) The harderian gland: a tercentennial review. J Anat 185 (Pt 1): 1.

    PubMed  PubMed Central  Google Scholar 

  19. Hu NF, Chang H, Du B, Zhang QW, et al. (2017) Tetramethylpyrazine ameliorated disuse-induced gastrocnemius muscle atrophy in hindlimb unloading rats through suppression of Ca(2+)/ROS-mediated apoptosis. Appl Physiol Nutr Metab 42: 117. https://doi.org/10.1139/apnm-2016-0363

  20. Biazik J, Vihinen H, Anwar T, Jokitalo E, et al. (2015) The versatile electron microscope: an ultrastructural overview of autophagy. Methods 75: 44. https://doi.org/10.1016/j.ymeth.2014.11.013

  21. Wang Z, Jiang SF, Cao J, Liu K, et al. (2019) Novel findings on ultrastructural protection of skeletal muscle fibers during hibernation of Daurian ground squirrels: Mitochondria, nuclei, cytoskeleton, glycogen. J Cell Physiol 234: 13318. https://doi.org/10.1002/jcp.28008

  22. Wang Z, Xu JH, Mou JJ, Kong XT, et al. (2020) Novel ultrastructural findings on cardiac mitochondria of huddling Brandt's voles in mild cold environment. Comp Biochem Physiol A Mol Integr Physiol 249: 110766. https://doi.org/10.1016/j.cbpa.2020.110766

  23. Mou J, Xu J, Wang Z, Wang C, et al. (2021) Effects of photoperiod on morphology and function in testis and epididymis of Cricetulus barabensis. J Cell Physiol 236: 2109. https://doi.org/10.1002/jcp.29998

  24. Li R, Shen Y (2013) An old method facing a new challenge: re-visiting housekeeping proteins as internal reference control for neuroscience research. Life Sci 92: 747. https://doi.org/10.1016/j.lfs.2013.02.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Posch A, Kohn J, Oh K, Hammond M, et al. (2013) V3 stain-free workflow for a practical, convenient, and reliable total protein loading control in western blotting. J Vis Exp 213: 50948. https://doi.org/10.3791/50948

  26. Marzuca-Nassr GN, Vitzel KF, Murata GM, Márquez JL, et al. (2019) Experimental Model of HindLimb Suspension-Induced Skeletal Muscle Atrophy in Rodents. Methods Mol Biol 1916: 167. https://doi.org/10.1007/978-1-4939-8994-2_16

  27. Alway SE, Siu PM (2008) Nuclear apoptosis contributes to sarcopenia. Exerc Sport Sci Rev 36: 51. https://doi.org/10.1097/JES.0b013e318168e9dc

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hao Y, Jackson JR, Wang Y, Edens N, et al. (2011) β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats. Am J Physiol Regul Integr Comp Physiol 301: R701. https://doi.org/10.1152/ajpregu.00840.2010

  29. Dewson G (2015) Investigating Bax subcellular localization and membrane integration. Cold Spring Harb Protoc 2015: 467. https://doi.org/10.1101/pdb.prot086447

    Article  PubMed  Google Scholar 

  30. Liao L X, Wang J K, Wan Y J, Liu Y, et al. (2020) Protosappanin A Maintains Neuronal Mitochondrial Homeostasis through Promoting Autophagic Degradation of Bax. Acs Chemical Neuroscience 11: 4223. https://doi.org/10.1021/acschemneuro.0c00488

  31. Hochhauser E, Kivity S, Offen D, Maulik N, et al. (2003) Bax ablation protects against myocardial ischemia-reperfusion injury in transgenic mice. American journal of physiology. Heart and circulatory physiology 284: H2351. https://doi.org/10.1152/ajpheart.00783.2002

  32. Kang M, Li S, Zhong D, Yang Z, et al. (2013) Hepatocyte apoptosis and mitochondrial permeability transition pore opening in rats with nonalcoholic fatty liver. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 33: 1062.

  33. Crouser ED, Julian MW, Huff JE, Joshi MS, et al. (2004) Abnormal permeability of inner and outer mitochondrial membranes contributes independently to mitochondrial dysfunction in the liver during acute endotoxemia. Crit Care Med 32: 478. https://doi.org/10.1097/01.CCM.0000109449.99160.81

  34. Michalska B, Duszyński J, Szymański J (2016) Mechanism of mitochondrial fission—structure and function of Drp1 protein. Postepy Biochem 62: 127.

    PubMed  Google Scholar 

  35. Fekkes P, Shepard KA, Yaffe MP (2000) Gag3p, an outer membrane protein required for fission of mitochondrial tubules. J Cell Biol 151: 333. https://doi.org/10.1083/jcb.151.2.333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang R, Wang G (2019) Autophagy in Mitochondrial Quality Control. Adv Exp Med Biol 1206: 421. https://doi.org/10.1007/978-981-15-0602-4_19

    Article  CAS  PubMed  Google Scholar 

  37. Ni HM, Williams JA, Ding WX (2015) Mitochondrial dynamics and mitochondrial quality control. Redox Biology 4: 6. https://doi.org/10.1016/j.redox.2014.11.006

    Article  CAS  PubMed  Google Scholar 

  38. Van Der Bliek AM, Shen Q, Kawajiri S (2013) Mechanisms of mitochondrial fission and fusion. Cold Spring Harb Perspect Biol 5: 1–17. https://doi.org/10.1101/cshperspect.a011072

    Article  CAS  Google Scholar 

  39. Meeusen S, Devay R, Block J, Cassidy-Stone A, et al. (2006) Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1. Cell 127: 383. https://doi.org/10.1016/j.cell.2006.09.021

  40. Wong ED, Wagner JA, Scott SV, Okreglak V, et al. (2003) The intramitochondrial dynamin-related GTPase, Mgm1p, is a component of a protein complex that mediates mitochondrial fusion. J Cell Biol 160: 303. https://doi.org/10.1083/jcb.200209015

  41. Suliman HB, Piantadosi CA (2016) Mitochondrial Quality Control as a Therapeutic Target. Pharmacol Rev 68: 20. https://doi.org/10.1124/pr.115.011502

    Article  CAS  PubMed  Google Scholar 

  42. Ji G, Chang H, Yang M, Chen H, et al. (2022) The mitochondrial proteomic changes of rat hippocampus induced by 28-day simulated microgravity. PLoS One 17: e0265108. https://doi.org/10.1371/journal.pone.0265108

Download references

Funding

This work was supported by funds from the National Natural Science Foundation of China (No. 32201276).

Author information

Authors and Affiliations

  1. School of Life Sciences, Qufu Normal University, Qufu, Shandong, China

    Xing-Chen Wang, Zhe Wang, Ya-Fei Chen, Le Chen, Bei-Ming Zhang, Rui Li, Yong-Zhen Feng, Li-Na Jiang & Jin-Hui Xu

Authors
  1. Xing-Chen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhe Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ya-Fei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Le Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bei-Ming Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yong-Zhen Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Li-Na Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jin-Hui Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

X.-C.W. and Z.W. conceived and designed the research; X.-C.W., Z.W., Y.-F.C., L.C., B.-M.Z., R.L., L.-N.J., and Y.-Z.F. performed the experiments; X.-C.W. analyzed the data; Z.W. interpreted the experimental results; X.-C.W. and Z.W. prepared the figures; X.-C.W., Z.W., and Y.-F.C. drafted the manuscript; and Z.W. and J.-H.X. edited the manuscript and approved the final version.

Corresponding authors

Correspondence to Zhe Wang or Jin-Hui Xu.

Ethics declarations

CONFLICT OF INTEREST

The authors declare the absence of obvious and potential conflicts of interest related to the publication of this article.

Additional information

Xing-Chen Wang and Zhe Wang contributed equally to this work.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1134/S0022093023040129.

10893_2023_8471_MOESM1_ESM.pdf

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, XC., Wang, Z., Chen, YF. et al. Stimulated Microgravity Affects Mitochondrial Homeostasis in the Harderian Glands of Mice. J Evol Biochem Phys 59, 1167–1181 (2023). https://doi.org/10.1134/S0022093023040129

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093023040129

Keywords:

Search

Navigation