Morphofunctional features in mice treated by low and high Hsp70 doses
https://doi.org/10.47093/2218-7332.2023.918.13
摘要
Aim. We sought to assess the effects of exogenous Hsp70 (single subcutaneous low- and high-dose injections) on organ structure and functions in adult mice.
Materials and methods. We randomized CD1 90-day-old male mice (n = 30) to three groups (10 mice per group). We injected the animals with single subcutaneous saline solution for Group 1 (control), low dose (500 μg/kg) of recombinant human Hsp70 (HspA1A) for Group 2, and high dose (5000 μg/kg) of the Hsp70 for Group 3. We examined the behavior of the mice on Day 3 after the injections (distance traveled, velocity, and bowel movement number). We lethalized the mice on Day 5 with further histological study and morphometrics of cerebral cortex, thymus, spleen, and liver. The statistics included one-factor ANOVA test with post hoc Tukey test.
Results. All study groups exhibited no significant difference of behavioral parameters. Some liver sinusoids were wider in control group and Hsp70 500 μg/kg group comparing to Hsp70 5000 μg/kg group. We obtained also data for morphometrics: no difference was found for the number of neurons in ganglionic cerebral cortex, the lymphocytic cellularity difference between thymic cortex and medulla, the number of lymphocytes in white splenic pulp, and the number of hepatocyte nuclei in the liver. Red splenic pulp exhibited 1774,5 ± 24,8, 1623,0 ± 26,7, 1553,6 ± 47,0 macrophages for control, low-dose and high-dose groups, respectively (р < 0,0001). Tukey test showed a significant difference between control group and each of Hsp70 groups 500 μg/kg (р = 0,012) and 5000 μg/kg (р < 0,0001).
Conclusion. Our study revealed no negative impact of subcutaneous Hsp70 administration at low and high doses on organ structure and functions in mice.
关于作者
G. Piavchenko俄罗斯联邦
A. Venediktov
俄罗斯联邦
E. Kuzmin
俄罗斯联邦
S. Kuznetsov
俄罗斯联邦
参考
1. Hagymasi A.T., Dempsey J.P., Srivastava P.K. Heat-Shock proteins. Curr Protoc. 2022; 2(11): e592. https://doi.org/10.1002/cpz1.592. PMID: 36367390
2. Albakova Z., Armeev G.A., Kanevskiy L.M., et al. HSP70 multifunctionality in cancer. Cells. 2020 Mar 2; 9(3): 587. https://doi.org/10.3390/cells9030587. PMID: 32121660
3. Roodveldt C., Outeiro T.F., Braun J.E.A. Editorial: Molecular Chaperones and neurodegeneration. Front Neurosci. 2017; 11: 565. https://doi.org/10.3389/fnins.2017.00565. PMID: 29085276
4. Магнаева А.С., Баранич Т.И., Воронков Д.Н. и др. Иммуногистохимическая оценка шаперон-индуцируемой аутофагии в различных отделах головного мозга человека при старении. Морфологические ведомости. 2023; 31(1): 724. https://doi.org/10.20340/mv-mn.2023.31(1).724
5. Юринская М.М., Фуников С.Ю., Евгеньев М.Б., Винокуров М.Г. Экзогенный белок теплового шока HSP70 снижает реакцию клеток нейробластомы человека на липополисахарид. Докл Биохим Биофизика. Июль 2016; 469(1): 239–243. https://doi.org/10.1134/S1607672916040025. Epub 2016 Sep 7. PMID: 27599502
6. Лазарев В.Ф., Дутышева Е.А., Утепова И.А. и др. Применение активаторов синтеза белков теплового шока в качестве нейропротекторов. III объединенный научный форум физиологов, биохимиков и молекулярных биологов. Материалы: VII съезд биохимиков России. X российский симпозиум «Белки и пептиды». VII съезд физиологов СНГ, Сочи, Дагомыс, 3–8 октября 2021 года. Том 2. М.: Издательство «Перо», 2021; 55–56. ISBN: 978-5-00189-678-4
7. Venediktov A., Bushueva O., Kudryavtseva V., et al. Closest horizons of Hsp70 engagement to manage neurodegeneration. Front. Mol. Neurosci. Sec. Molecular Signalling and Pathways. 2023;16. https://doi.org/10.3389/fnmol.2023.1230436
8. Zatsepina O.G., Evgen’ev M.B., Garbuz D.G. Role of a Heat Shock transcription factor and the major Heat Shock protein Hsp70 in memory formation and neuroprotection. Cells. 2021; 10: 1638. https://doi.org/10.3390/cells10071638. PMID: 34210082
9. Kalmar B., Greensmith L. Cellular chaperones as therapeutic targets in ALS to restore protein homeostasis and improve cellular function. Front Mol Neurosci. 2017; 10(9): 251. https://doi.org/10.3389/fnmol.2017.00251
10. Festing M.F.W., Altman D.G. Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR J. 2002; 43(4): 244–258. https://doi.org/10.1093/ilar.43.4.244. Erratum in: ILAR J. 2005; 46(3): 320. PMID: 12391400
11. Baran-Gale J., Morgan M.D., Maio S., et al. Ageing compromises mouse thymus function and remodels epithelial cell differentiation. Elife. 2020; 9: e56221. https://doi.org/10.7554/eLife.56221. PMID: 32840480
12. Yousefzadeh M.J., Zhao J., Bukata C., et al. Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice. Aging Cell. 2020 Mar; 19 (3): e13094. https://doi.org/10.1111/acel.13094. Epub 2020 Jan 25. PMID: 31981461
13. Rai R., Kennedy A.L., Isingizwe Z.R., et al. Similarities and differences of Hsp70, Hsc70, Grp78, and mortalin as cancer biomarkers and drug targets. Cells. 2021; 10(11): 2996. https://doi.org/10.3390/cells10112996. PMID: 34831218
14. Moody C.M., Makowska I.J., Weary D.M. Testing three measures of mouse insensibility following induction with isoflurane or carbon dioxide gas for a more humane euthanasia. Applied Animal Behaviour Science. 2015; 163: 183–187. https://doi.org/10.1016/J.APPLANIM.2014.11.010
15. Feldman A.T., Wolfe D. Tissue processing and hematoxylin and eosin staining. Methods Mol Biol. 2014; 1180: 31–43. https://doi.org/10.1007/978-1-4939-1050-2_3. PMID: 25015141
16. Bankhead P., Loughrey M.B., Fernández J.A., et al. QuPath: Open-source software for digital pathology image analysis. Sci Rep. 2017; 7(1): 16878. https://doi.org/10.1038/s41598-017-17204-5. PMID: 29203879
17. Lee C.H., Su T.C., Lee M.S., et al. Heat shock protein 70 protects the lungs from hyperoxic injury in a neonatal rat model of bronchopulmonary dysplasia. PLoS One. 2023; 18(5): e0285944. https://doi.org/10.1371/journal.pone.0285944. PMID: 37200358
18. Son H., Choi H.S., Baek S.E., et al. Shear stress induces monocyte/ macrophage-mediated inflammation by upregulating cell-surface expression of heat shock proteins. Biomed Pharmacother. 2023; 161: 114566. https://doi.org/10.1016/j.biopha.2023.114566. Epub 2023 Mar 22. PMID: 36963359
19. Yamaguchi-Tanaka M., Takagi K., Miki Y., et al. The pro-tumorigenic role of chemotherapy-induced extracellular HSP70 from breast cancer cells via intratumoral macrophages. Cancers (Basel). 2023; 15(6): 1903. https://doi.org/10.3390/cancers15061903. PMID: 36980788
20. Kao J.K., Hsu T.F., Lee M.S., et al. Subcutaneous injection of recombinant heat shock protein 70 ameliorates atopic dermatitis skin lesions in a mouse model. Kaohsiung J Med Sci. 2020; 36(3): 186-195. https://doi.org/10.1002/kjm2.12163. Epub 2020 Jan 6. PMID: 31904187
21. Bobkova N.V., Evgen’ev M., Garbuz D.G., et al. Exogenous Hsp70 delays senescence and improves cognitive function in aging mice. Proc Natl Acad Sci USA. 2015; 112(52): 16006–16011. https://doi.org/10.1073/pnas.1516131112. Epub 2015 Dec 14. PMID: 26668376
22. Yurinskaya M.M., Kochetkova O.Y., Shabarchina L.I., et al. Encapsulated Hsp70 decreases endotoxin-induced production of ROS and TNFα in human phagocytes. Cell Stress Chaperones. 2017; 22(1): 163–171. https://doi.org/10.1007/s12192-016-0743-z. Epub 2016 Oct 26. Erratum in: Cell Stress Chaperones. 2017 Mar; 22(2): 317. PMID: 27783274
补充文件
![]() |
1. The ARRIVE guidelines 2.0: author checklist | |
主题 | ||
类型 | Исследовательские инструменты | |
下载
(163KB)
|
索引源数据 ▾ |