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Target Concepts:
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Query: UMLS:C0848237 (
acute stress
)
4,619
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cells respond to environmental stress with activation of c-Jun N-terminal kinase (JNK) and p38. Recent studies have implicated Gadd45 and two related proteins, MyD118/Gadd45beta and CR6/Gadd45gamma, as initiators of JNK/p38 signaling via their interaction with an upstream kinase MTK1. It was proposed that stress-induced expression of the Gadd45-related proteins leads to MTK1 activation and subsequent JNK/p38 activation. Using embryo fibroblasts from gadd45-null mice, we have addressed the requirement for Gadd45 in mediating JNK/p38 activation during
acute stress
. Comparison of JNK/p38 activities in response to
methyl methanesulfonate
, hydrogen peroxide, UVC irradiation, sorbitol, and anisomycin treatment of gadd45(+/+) and gadd45(-/-) fibroblasts revealed no deficiency in JNK/p38 activation in gadd45(-/-) fibroblasts. In addition, in wild type cells, JNK and p38 activation significantly preceded gadd45 induction with all stresses. Examination of myd118/gadd45beta and cr6/gadd45gamma expression in gadd45(+/+) and gadd45(-/-) fibroblasts revealed similar induction patterns in the two cell types, which, like gadd45 expression, was delayed relative to JNK/p38 activation. We conclude that gadd45 expression is not required for activation of JNK/p38 by environmental stresses, nor are stress-induced increases in myd118/gadd45beta and cr6/gadd45gamma expression necessary for kinase activation in response to such insults.
...
PMID:gadd45 is not required for activation of c-Jun N-terminal kinase or p38 during acute stress. 1051 26
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
