Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0848237 (
acute stress
)
4,619
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The cellular prion protein PrP
C
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 PrP
C
. Clearly, this protein operates in highly diverse cellular contexts. Investigations into putative stress-protective roles for PrP
C
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 PrP
C
(
PRNP
Ter/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 Cu
2+
ions, as well as levels of reactive oxygen species (ROS) after exposure to FeSO
4
and H
2
O
2
. Surprisingly, PrP
C
-negative spermatozoa reacted similarly to normal spermatozoa in all read-outs. Moreover,
in vitro
exposure of PBMCs to
Doxorubicin
, H
2
O
2
and methyl methanesulfonate (MMS), revealed no effect of PrP
C
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 PrP
C
. RNA sequencing of PBMCs (
n
= 8 of
PRNP
+/+
and
PRNP
Ter/Ter
) showed that basal level expression of genes encoding DNA repair enzymes, ROS scavenging, and antioxidant enzymes were unaffected by the absence of PrP
C
. Data presented here questions the
in vitro
cytoprotective roles previously attributed to PrP
C
, although not excluding such functions in other cell types or tissues during inflammatory stress.
...
PMID:Stress Resilience of Spermatozoa and Blood Mononuclear Cells without Prion Protein. 2941 49
