4 research outputs found
Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy
Abstract Cardiac physiology and hypertrophy are regulated
by the phosphorylation status of many proteins, which
is partly controlled by a poorly defined type 2A protein
phosphatase-alpha4 intracellular signalling axis. Quantitative
PCR analysis revealed that mRNA levels of the type
2A catalytic subunits were differentially expressed in H9c2
cardiomyocytes (PP2ACb[PP2ACa[PP4C[PP6C),
NRVM (PP2ACb[PP2ACa = PP4C = PP6C), and
adult rat ventricular myocytes (PP2ACa[
PP2ACb[PP6C[PP4C). Western analysis confirmed
that all type 2A catalytic subunits were expressed in H9c2
cardiomyocytes; however, PP4C protein was absent in
adult myocytes and only detectable following 26S proteasome
inhibition. Short-term knockdown of alpha4 protein
expression attenuated expression of all type 2A catalytic
subunits. Pressure overload-induced left ventricular (LV)
hypertrophy was associated with an increase in both
PP2AC and alpha4 protein expression. Although PP6C
expression was unchanged, expression of PP6C regulatory
subunits (1) Sit4-associated protein 1 (SAP1) and (2)
ankyrin repeat domain (ANKRD) 28 and 44 proteins was
elevated, whereas SAP2 expression was reduced in
hypertrophied LV tissue. Co-immunoprecipitation studies
demonstrated that the interaction between alpha4 and
PP2AC or PP6C subunits was either unchanged or reduced
in hypertrophied LV tissue, respectively. Phosphorylation
status of phospholemman (Ser63 and Ser68) was significantly
increased by knockdown of PP2ACa, PP2ACb, or
PP4C protein expression. DNA damage assessed by histone
H2A.X phosphorylation (cH2A.X) in hypertrophied tissue
remained unchanged. However, exposure of cardiomyocytes
to H2O2 increased levels of cH2A.X which was
unaffected by knockdown of PP6C expression, but was
abolished by the short-term knockdown of alpha4 expression.
This study illustrates the significance and altered
activity of the type 2A protein phosphatase-alpha4 complex
in healthy and hypertrophied myocardium
How many are there? Multiple-covariate distance sampling for monitoring pampas deer in Corrientes, Argentina
Feeding habits of a large endangered skate from the south-west Atlantic: the spotback skate, Atlantoraja castelnaui
Live or let die: The cell's response to p53
Compared with many normal tissues, cancer cells are highly sensitized to apoptotic signals, and survive only because they have acquired lesions — such as loss of p53 — that prevent or impede cell death. We are now beginning to understand the complex mechanisms that regulate whether or not a cell dies in response to p53 — insights that will ultimately contribute to the development of therapeutic strategies to repair the apoptotic p53 response in cancers