Skip to main content
Log in

Nano-selenium Antagonizes Heat Stress-Induced Apoptosis of Rainbow Trout (Oncorhynchus mykiss) Hepatocytes by Activating the PI3K/AKT Pathway

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The cold-water fish rainbow trout (Oncorhynchus mykiss) shows poor resistance to heat, which is the main factor restricting their survival and yield. With the advancement of nanotechnology, nano-selenium (nano-Se) has emerged as a key nano-trace element, showing unique advantages, including high biological activity and low toxicity, for studying the response of animals to adverse environmental conditions. However, little is still known regarding the potential protective mechanisms of nano-Se against heat stress-induced cellular damage. Herein, we aimed to investigate the mechanism underlying the antagonistic effects of nano-Se on heat stress. Four groups were assessed: CG18 (0 μg/mL nano-Se, 18 °C), Se18 (5.0 μg/mL nano-Se, 18 °C), CG24 (0 μg/mL nano-Se, incubated at 18 °C for 24 h and then transferred to 24 °C culture), and Se24 (5.0 μg/mL nano-Se, incubated at 18 °C for 24 h and then transferred to 24 °C culture). We found that after heat treatment (CG24 group), T-AOC, GPx, and CAT activities in rainbow trout hepatocytes showed a decrease of 36%, 33%, and 19%, respectively, while ROS and MDA levels showed an increase of 67% and 93%, respectively (P < 0.05). Meanwhile, the mRNA levels of the apoptosis-related genes caspase3, caspase9, Cyt-c, Bax, and Bax/Bcl-2 in the CG24 group were 41%, 47%, 285%, 65%, and 151% higher than those in the CG18 group, respectively, while those of PI3K and AKT were 31% and 17% lower, respectively (P < 0.05). Besides, flow cytometry analysis showed an increase in the level of apoptotic cells after heat exposure. More importantly, we observed that nano-Se cotreatment (Se24 group) remarkably attenuated heat stress-induced effects (P < 0.05). We conclude that heat stress induces oxidative stress and apoptosis in rainbow trout hepatocytes. Nano-Se ameliorates heat stress-induced apoptosis by activating the PI3K/AKT pathway. Our results provide a new perspective to improve our understanding of the ability of nano-Se to confer heat stress resistance.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

Data Availability

The data of this study will be made available on reasonable request.

Code Availability

Not applicable.

References

  1. Alfonso S, Gesto M, Sadoul B (2021) Temperature increase and its effects on fish stress physiology in the context of global warming. J Fish Biol 98(6):1496–1508. https://doi.org/10.1111/jfb.14599

    Article  PubMed  Google Scholar 

  2. Chokshi K, Pancha I, Trivedi K, Maurya R, Ghosh A, Mishra S (2020) Physiological responses of the green microalga Acutodesmus dimorphus to temperature induced oxidative stress conditions. Physiol Plant 170(4):462–473. https://doi.org/10.1111/ppl.13193

    Article  CAS  PubMed  Google Scholar 

  3. Semmouri I, Asselman J, Van Nieuwerburgh F, Deforce D, Janssen CR, De Schamphelaere K (2019) The transcriptome of the marine calanoid copepod Temora longicornis under heat stress and recovery. Mar Environ Res 143:10–23. https://doi.org/10.1016/j.marenvres.2018.10.017

    Article  CAS  PubMed  Google Scholar 

  4. Quan J, Kang Y, Luo Z, Zhao G, Ma F, Li L, Liu Z (2020) Identification and characterization of long noncoding RNAs provide insight into the regulation of gene expression in response to heat stress in rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol Part D Genomics Proteomics 36:100707. https://doi.org/10.1016/j.cbd.2020.100707

    Article  CAS  PubMed  Google Scholar 

  5. Heath ME, Ridgway SH (1999) How dolphins use their blubber to avoid heat stress during encounters with warm water. Am J Physiol 276(4):R1188–R1194. https://doi.org/10.1152/ajpregu.1999.276.4.R1188

    Article  CAS  PubMed  Google Scholar 

  6. Clarke A, Johnston NM (1999) Scaling of metabolic rate with body mass and temperature in teleost fish. J Anim Ecol 68(5):893–905. https://doi.org/10.1046/j.1365-2656.1999.00337.x

    Article  Google Scholar 

  7. Pörtner HO, Knust R (2007) Climate change affects marine fishes through the oxygen limitation of thermal tolerance. Science 315(5808):95–97. https://doi.org/10.1126/science.1135471

    Article  CAS  PubMed  Google Scholar 

  8. Giacomin M, Schulte PM, Wood CM (2017) Differential effects of temperature on oxygen consumption and branchial fluxes of urea, ammonia, and water in the dogfish shark (Squalus acanthias suckleyi). Physiol Biochem Zool 90(6):627–637. https://doi.org/10.1086/694296

    Article  PubMed  Google Scholar 

  9. Enzor LA, Zippay ML, Place SP (2013) High latitude fish in a high CO2 world: synergistic effects of elevated temperature and carbon dioxide on the metabolic rates of Antarctic notothenioids. Comp Biochem Physiol A Mol Integr Physiol 164(1):154–161. https://doi.org/10.1016/j.cbpa.2012.07.016

  10. Wang Y, Li X, Yao Y, Zhao X, Shi X, Cai Y (2021) Selenium deficiency induces apoptosis and necroptosis through ROS/MAPK signal in human uterine smooth muscle cells. Biol Trace Elem Res 200(7):3147–3158. https://doi.org/10.1007/s12011-021-02910-z

    Article  CAS  PubMed  Google Scholar 

  11. Hamilton SJ (2004) Review of selenium toxicity in the aquatic food chain. Sci Total Environ 326(1–3):1–31. https://doi.org/10.1016/j.scitotenv.2004.01.019

    Article  CAS  PubMed  Google Scholar 

  12. Sarkar B, Bhattacharjee S, Daware A, Tribedi P, Krishnani KK, Minhas PS (2015) Selenium nanoparticles for stress-resilient fish and livestock. Nanoscale Res Lett 10(1):371. https://doi.org/10.1186/s11671-015-1073-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang H, Zhang J, Yu H (2007) Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice. Free Radic Biol Med 42(10):1524–1533. https://doi.org/10.1016/j.freeradbiomed.2007.02.013

    Article  CAS  PubMed  Google Scholar 

  14. Zhang JS, Gao XY, Zhang LD, Bao YP (2001) Biological effects of a nano red elemental selenium. BioFactors 15(1):27–38. https://doi.org/10.1002/biof.5520150103

    Article  PubMed  Google Scholar 

  15. Sun J, Liu Z, Quan J, Li L, Zhao G, Lu J (2021) Protective effects of different concentrations of selenium nanoparticles on rainbow trout (Oncorhynchus mykiss) primary hepatocytes under heat stress. Ecotoxicol Environ Saf 230:113121. https://doi.org/10.1016/j.ecoenv.2021.113121

    Article  CAS  PubMed  Google Scholar 

  16. Naiel M, Negm SS, Abd El-Hameed S, Abdel-Latif H (2021) Dietary organic selenium improves growth, serum biochemical indices, immune responses, antioxidative capacity, and modulates transcription of stress-related genes in Nile tilapia reared under sub-optimal temperature. J Therm Biol 99:102999. https://doi.org/10.1016/j.jtherbio.2021.102999

    Article  CAS  PubMed  Google Scholar 

  17. Liu D, Xu J, Qian G, Hamid M, Gan F, Chen X, Huang K (2018) Selenizing astragalus polysaccharide attenuates PCV2 replication promotion caused by oxidative stress through autophagy inhibition via PI3K/AKT activation. Int J Biol Macromol 108:350–359. https://doi.org/10.1016/j.ijbiomac.2017.12.010

    Article  CAS  PubMed  Google Scholar 

  18. Ji K, Liang H, Ren M, Ge X, Mi H, Pan L, Yu H (2020) The immunoreaction and antioxidant capacity of juvenile blunt snout bream (Megalobrama amblycephala) involves the PI3K/Akt/Nrf2 and NF-κB signal pathways in response to dietary methionine levels. Fish Shellfish Immunol 105:126–134. https://doi.org/10.1016/j.fsi.2020.07.005

    Article  CAS  PubMed  Google Scholar 

  19. Gobé G, Zhang XJ, Willgoss DA, Schoch E, Hogg NA, Endre ZH (2000) Relationship between expression of Bcl-2 genes and growth factors in ischemic acute renal failure in the rat. J Am Soc Nephrol 11(3):454–467. https://doi.org/10.1681/ASN.V113454

    Article  PubMed  Google Scholar 

  20. Jin X, Jia T, Liu R, Xu S (2018) The antagonistic effect of selenium on cadmium-induced apoptosis via PPAR-γ/PI3K/Akt pathway in chicken pancreas. J Hazard Mater 357:355–362. https://doi.org/10.1016/j.jhazmat.2018.06.003

    Article  CAS  PubMed  Google Scholar 

  21. Wang C, Gu Z, Gu X, Tan X, Wang S, Zhang R, Li R, Sun M, Gui C, Li S, Ye Y, Ma J, Su L, Liang C (2022) Nano-selenium attenuates mitochondrial-associated apoptosis via the PI3K/AKT pathway in nickel-induced hepatotoxicity in vivo and in vitro. Environ Toxicol 37(1):101–119. https://doi.org/10.1002/tox.23381

    Article  CAS  PubMed  Google Scholar 

  22. Li P, Li K, Zou C, Tong C, Sun L, Cao Z, Yang S, Lyu Q (2020) Selenium yeast alleviates ochratoxin a-induced hepatotoxicity via modulation of the PI3K/AKT and Nrf2/Keap1 signaling pathways in chickens. Toxins 12(3):143. https://doi.org/10.3390/toxins12030143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chen SJ, Zhang CY, Yu D, Lin CJ, Xu HJ, Hu CM (2022) Selenium alleviates inflammation in staphylococcus aureus-induced mastitis via MerTK-dependent activation of the PI3K/Akt/mTOR pathway in mice. Biol Trace Elem Res 200(4):1750–1762. https://doi.org/10.1007/s12011-021-02794-z

    Article  CAS  PubMed  Google Scholar 

  24. Thorgaard GH, Bailey GS, Williams D, Buhler DR, Kaattari SL, Ristow SS, Hansen JD, Winton JR, Bartholomew JL, Nagler JJ, Walsh PJ, Vijayan MM, Devlin RH, Hardy RW, Overturf KE, Young WP, Robison BD, Rexroad C, Palti Y (2002) Status and opportunities for genomics research with rainbow trout. Comp Biochem Physiol B Biochem Mol Biol 133(4):609–646. https://doi.org/10.1016/s1096-4959(02)00167-7

    Article  PubMed  Google Scholar 

  25. Hazel JR (1979) Influence of thermal acclimation on membrane lipid composition of rainbow trout liver. Am J Physiol 236(1):R91–R101. https://doi.org/10.1152/ajpregu.1979.236.1.R91

    Article  CAS  PubMed  Google Scholar 

  26. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt Method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262

  27. Belhadj Slimen I, Najar T, Ghram A, Abdrrabba M (2016) Heat stress effects on livestock: molecular, cellular and metabolic aspects, a review. J Anim Physiol Anim Nutr (Berl) 100(3):401–412. https://doi.org/10.1111/jpn.12379

    Article  CAS  PubMed  Google Scholar 

  28. Neamat-Allah A, Mahmoud EA, Abd El Hakim Y (2019) Efficacy of dietary Nano-selenium on growth, immune response, antioxidant, transcriptomic profile and resistance of Nile tilapia, Oreochromis niloticus against Streptococcus iniae infection. Fish Shellfish Immunol 94:280–287. https://doi.org/10.1016/j.fsi.2019.09.019

    Article  CAS  PubMed  Google Scholar 

  29. Li L, Liu Z, Quan J, Sun J, Lu J, Zhao G (2022) Comprehensive proteomic analysis to elucidate the anti-heat stress effects of nano-selenium in rainbow trout (Oncorhynchus mykiss). Ecotoxicol Environ Saf 241:113736. https://doi.org/10.1016/j.ecoenv.2022.113736

    Article  CAS  PubMed  Google Scholar 

  30. Misra S, Niyogi S (2009) Selenite causes cytotoxicity in rainbow trout (Oncorhynchus mykiss) hepatocytes by inducing oxidative stress. Toxicol In Vitro 23(7):1249–1258. https://doi.org/10.1016/j.tiv.2009.07.031

    Article  CAS  PubMed  Google Scholar 

  31. Bernet D, Schmidt H, Meier W, Burkhardt-Holm P, Wahli T (1999) Histopathology in fish: proposal for a protocol to assess aquatic pollution. J Fish Dis 22:25–34. https://doi.org/10.1046/j.1365-2761.1999.00134.x

    Article  Google Scholar 

  32. Yu H, Zhang C, Zhang X, Wang C, Li P, Liu G, Yan X, Xiong X, Zhang L, Hou J, Liu S, Zhou J, Ji H (2020) Dietary nano-selenium enhances antioxidant capacity and hypoxia tolerance of grass carp Ctenopharyngodon idella fed with high-fat diet. Aquacult Nutr 26(2):545–557. https://doi.org/10.1111/anu.13016

    Article  CAS  Google Scholar 

  33. Wang Y, Yan X, Fu L (2013) Effect of selenium nanoparticles with different sizes in primary cultured intestinal epithelial cells of crucian carp, Carassius auratus gibelio. Int J Nanomedicine 8:4007–4013. https://doi.org/10.2147/IJN.S43691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Slimen IB, Najar T, Ghram A, Dabbebi H, Ben Mrad M, Abdrabbah M (2014) Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review. Int J Hyperthermia 30(7):513–523. https://doi.org/10.3109/02656736.2014.971446

    Article  CAS  PubMed  Google Scholar 

  35. Kieliszek M, Błażejak S (2013) Selenium: Significance, and outlook for supplementation. Nutrition 29(5):713–718. https://doi.org/10.1016/j.nut.2012.11.012

    Article  CAS  PubMed  Google Scholar 

  36. Khan AZ, Khan IU, Khan S, Afzal S, Hamid M, Tariq M, Haq IU, Ullah N, Khan MA, Bilal S, Huwang K, Liu R (2019) Selenium-enriched probiotics improve hepatic protection by regulating pro-inflammatory cytokines and antioxidant capacity in broilers under heat stress conditions. J Adv Vet Anim Res 6(3):355–361. https://doi.org/10.5455/javar.2019.f354

    Article  PubMed  PubMed Central  Google Scholar 

  37. Sinha K, Das J, Pal PB, Sil PC (2013) Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol 87(7):1157–1180. https://doi.org/10.1007/s00204-013-1034-4

    Article  CAS  PubMed  Google Scholar 

  38. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516. https://doi.org/10.1080/01926230701320337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443(7113):787–795. https://doi.org/10.1038/nature05292

    Article  CAS  PubMed  Google Scholar 

  40. Liu E, Zhao X, Li C, Wang Y, Li L, Zhu H, Ling Q (2022) Effects of acute heat stress on liver damage, apoptosis and inflammation of pikeperch (Sander lucioperca). J Therm Biol 106:103251. https://doi.org/10.1016/j.jtherbio.2022.103251

    Article  CAS  PubMed  Google Scholar 

  41. Chen F, Ling X, Zhao Y, Fu S (2022) Hypoxia-induced oxidative stress and apoptosis in gills of scaleless carp (Gymnocypris przewalskii). Fish Physiol Biochem 48(4):911–924. https://doi.org/10.1007/s10695-022-01091-3

    Article  CAS  PubMed  Google Scholar 

  42. Chen G, Wang L, Li W, Zhang Q, Hu T (2020) Nodularin induced oxidative stress contributes to developmental toxicity in zebrafish embryos. Ecotoxicol Environ Saf 194:110444. https://doi.org/10.1016/j.ecoenv.2020.110444

    Article  CAS  PubMed  Google Scholar 

  43. Jia R, Du J, Cao L, Feng W, He Q, Xu P, Yin G (2020) Chronic exposure of hydrogen peroxide alters redox state, apoptosis and endoplasmic reticulum stress in common carp (Cyprinus carpio). Aquat Toxicol 229:105657. https://doi.org/10.1016/j.aquatox.2020.105657

    Article  CAS  PubMed  Google Scholar 

  44. Li H, Zhang J, Xia Y, Pan W, Zhou D (2021) Antagonistic effect of nano-selenium on hepatocyte apoptosis induced by DEHP via PI3K/AKT pathway in chicken liver. Ecotoxicol Environ Saf 218:112282. https://doi.org/10.1016/j.ecoenv.2021.112282

    Article  CAS  PubMed  Google Scholar 

  45. Zhao G, Qi L, Wang Y, Li X, Li Q, Tang X, Wang X, Wu C (2021) Antagonizing effects of curcumin against mercury-induced autophagic death and trace elements disorder by regulating PI3K/AKT and Nrf2 pathway in the spleen. Ecotoxicol Environ Saf 222:112529. https://doi.org/10.1016/j.ecoenv.2021.112529

    Article  CAS  PubMed  Google Scholar 

  46. Wu Y, Qin D, Yang H, Wang W, Xiao J, Zhou L, Fu H (2020) Neuroprotective effects of deuterium-depleted water (DDW) against H2O2-induced oxidative stress in differentiated PC12 cells through the PI3K/Akt signaling pathway. Neurochem Res 45(5):1034–1044. https://doi.org/10.1007/s11064-020-02978-4

  47. Gao Z, Liu F, Yin P, Wan C, He S, Liu X, Zhao H, Liu T, Xu J, Guo S (2013) Inhibition of heat-induced apoptosis in rat small intestine and IEC-6 cells through the AKT signaling pathway. BMC Vet Res 9:241. https://doi.org/10.1186/1746-6148-9-241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Li XL, Wong YS, Xu G, Chan JC (2015) Selenium-enriched Spirulina protects INS-1E pancreatic beta cells from human islet amyloid polypeptide-induced apoptosis through suppression of ROS-mediated mitochondrial dysfunction and PI3/AKT pathway. Eur J Nutr 54(4):509–522. https://doi.org/10.1007/s00394-014-0732-x

    Article  CAS  PubMed  Google Scholar 

  49. Xiong X, Zhang Y, Xing H, Xu S (2020) Ameliorative effect of selenomethionine on cadmium-induced hepatocyte apoptosis via regulating PI3K/AKT pathway in chickens. Biol Trace Elem Res 195(2):559–568. https://doi.org/10.1007/s12011-019-01858-5

    Article  CAS  PubMed  Google Scholar 

  50. Sato S, Fujita N, Tsuruo T (2000) Modulation of Akt kinase activity by binding to Hsp90. Proc Natl Acad Sci U S A 97(20):10832–10837. https://doi.org/10.1073/pnas.170276797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gao F, Hu XY, Xie XJ, Xu QY, Wang YP, Liu XB, Xiang MX, Sun Y, Wang JA (2010) Heat shock protein 90 protects rat mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the PI3K/Akt and ERK1/2 pathways. J Zhejiang Univ Sci B 11(8):608–617. https://doi.org/10.1631/jzus.B1001007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang J, Wang X, Vikash V, Ye Q, Wu D, Liu Y, Dong W (2016) ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev 2016:4350965. https://doi.org/10.1155/2016/4350965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Leslie NR, Downes CP (2002) PTEN: The down side of PI 3-kinase signalling. Cell Signal 14(4):285–295. https://doi.org/10.1016/s0898-6568(01)00234-0

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 31960727).

Author information

Authors and Affiliations

Authors

Contributions

Lanlan Li is responsible for the conceptualization, methodology, writing—original draft, and writing—review and editing. Zhe Liu did writing—review and editing—and supervision. Jinqiang Quan is assigned to data curation. Jun Sun is assigned to methodology and investigation. Guiyan Zhao is involved in data curation, software, and conceptualization. Junhao Lu is the checking. All authors approved the final manuscript.

Corresponding author

Correspondence to Zhe Liu.

Ethics declarations

Competing Interests

The authors declare no competing interests.

Ethics Approval and Consent to Participate

All the experiments were performed in accordance with the Chinese Legislation on the Use and Care of Laboratory Animals, and the protocol was approved by the Ethics Committee at Gansu Agricultural University (No. GSAU-2019–52).

Competing Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLS 23 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, L., Liu, Z., Zhao, G. et al. Nano-selenium Antagonizes Heat Stress-Induced Apoptosis of Rainbow Trout (Oncorhynchus mykiss) Hepatocytes by Activating the PI3K/AKT Pathway. Biol Trace Elem Res 201, 5805–5815 (2023). https://doi.org/10.1007/s12011-023-03637-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-023-03637-9

Keywords

Navigation