Stress Resilience of Spermatozoa and Blood Mononuclear Cells without Prion Protein

Frontiers in Molecular Biosciences

Anna Kusnierczyk¹  Teklu T. Zeremichael²  Elisabeth Kommisrud²  Frøydis D. Myromslien²  Else-Berit Stenseth²  Liv Heidi Nekså³  Gunn C. Østby³  Maren K. Bakkebø³  Arild Espenes³  Michael A. Tranulis³  Clara M. O. Jalland³  Malin R. Reiten³  Anette K. Krogenæs³  Giulia Malachin³  Susan S. Røed³  Magnar Bjørås⁴  Karin E. Waterhouse⁴ 

[1] Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway;Faculty of Education and Natural Sciences, Inland University of Applied Sciences, Hamar, Norway;Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway;Spermvital AS Holsetgata, Hamar, Norway;

关键词: prion protein;    stress resilience;    spermatocytes;    peripheral blood mononuclear cells;    goat model;    testes;   

DOI  :  10.3389/fmolb.2018.00001

来源: DOAJ

【 摘 要 】

The cellular prion protein PrPC is highly expressed in neurons, but also present in non-neuronal tissues, including the testicles and spermatozoa. Most immune cells and their bone marrow precursors also express PrPC. Clearly, this protein operates in highly diverse cellular contexts. Investigations into putative stress-protective roles for PrPC have resulted in an array of functions, such as inhibition of apoptosis, stimulation of anti-oxidant enzymes, scavenging roles, and a role in nuclear DNA repair. We have studied stress resilience of spermatozoa and peripheral blood mononuclear cells (PBMCs) derived from non-transgenic goats that lack PrPC (PRNPTer/Ter) compared with cells from normal (PRNP+/+) goats. Spermatozoa were analyzed for freeze tolerance, DNA integrity, viability, motility, ATP levels, and acrosome intactness at rest and after acute stress, induced by Cu2+ ions, as well as levels of reactive oxygen species (ROS) after exposure to FeSO4 and H2O2. Surprisingly, PrPC-negative spermatozoa reacted similarly to normal spermatozoa in all read-outs. Moreover, in vitro exposure of PBMCs to Doxorubicin, H2O2 and methyl methanesulfonate (MMS), revealed no effect of PrPC on cellular survival or global accumulation of DNA damage. Similar results were obtained with human neuroblastoma (SH-SY5Y) cell lines stably expressing varying levels of PrPC. RNA sequencing of PBMCs (n = 8 of PRNP+/+ and PRNPTer/Ter) showed that basal level expression of genes encoding DNA repair enzymes, ROS scavenging, and antioxidant enzymes were unaffected by the absence of PrPC. Data presented here questions the in vitro cytoprotective roles previously attributed to PrPC, although not excluding such functions in other cell types or tissues during inflammatory stress.

【 授权许可】

Unknown