Biomedical subjects

Katy E Beck

Publications and source records attributed to Katy E Beck.

4 recordsLinked to original sources

PubMed2006

The role of tissue transglutaminase in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in differentiated human SH-SY5Y neuroblastoma cells.

Tissue transglutaminase (TG2) can induce post-translational modification of proteins, resulting in protein cross-linking or incorporation of polyamines into substrates, and can also function as a signal transducing G protein. The role of TG2 in the formation of insoluble cross-links has led to its implication in some neurodegenerative conditions. Exposure of pre-differentiated SH-SY5Y cells to the Parkinsonian neurotoxin 1-methyl-4-phenylpyridinium ion (MPP(+)) resulted in significant dose-dependent reductions in TG2 protein levels, measured by probing Western blots with a TG2-specific antibody. Transglutaminase (TG) transamidating activity, on the other hand, monitored by incorporation of a polyamine pseudo-substrate into cellular proteins, was increased. Inhibitors of TG (putrescine) and TG2 (R283) exacerbated MPP(+) toxicity, suggesting that activation of TG2 may promote a survival response in this toxicity paradigm.

1-Methyl-4-phenylpyridinium↗

PubMed2006

The cysteine string protein multimeric complex.

Cysteine string protein (CSPalpha) is a member of the cellular folding machinery that is located on regulated secretory vesicles. We have previously shown that CSPalpha in association with Hsc70 (70kDa heat shock cognate protein) and SGT (small glutamine-rich tetratricopeptide repeat domain protein) is a guanine nucleotide exchange factor (GEF) for G(alphas). Association of this CSPalpha complex with N-type calcium channels, a channel key in coupling calcium influx with synaptic vesicle exocytosis, triggers tonic G protein inhibition of the channels. Syntaxin 1A, a plasma membrane SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) critical for neurotransmission, coimmunoprecipitates with the CSPalpha/G protein/N-type calcium channel complex, however the significance of syntaxin 1A as a component of this complex remains unknown. In this report, we establish that syntaxin 1A interacts with CSPalpha, Hsc70 as well as the synaptic protein interaction (synprint) region of N-type channels. We demonstrate that huntingtin(exon1), a putative biologically active fragment of huntingtin, displaces both syntaxin 1A and CSPalpha from N-type channels. Identification of the protein components of the CSPalpha/GEF system is essential in establishing its precise role in synaptic transmission.

Animals↗

PubMed2006

Rdj2, a J protein family member, interacts with cellular prion PrP(C).

PrP(C) is a glycosylphosphatidylinositol (GPI) anchored glycoprotein of unknown function. Misfolding of normal cellular PrP(C) to the pathogenic PrP(Sc) is the hallmark of prion diseases (transmissible spongiform encephalopathies). Prion diseases are characterized by extensive neurodegeneration and early death. Understanding how PrP(C) maintains its correct conformation is a major endeavor of current inquiry. Here we demonstrate a novel interaction between PrP(C) and the J protein family member, Rdj2 (DjA2; Dj3, Dnj3, Cpr3, and Hirip4). The importance of the J protein family in the cellular folding machinery has been recognized for many years. The PrP(C)/Rdj2 association was direct and concentration-dependent. Other J proteins such as CSPalpha and auxilin did not associate with PrP(C) in the absence of ATP, demonstrating the specificity of the PrP(C)/J protein interaction. These findings suggest that the J protein family serves as a 'folding catalyst' for PrP(C) and implicates Rdj2 as a factor in the protection against prion diseases.

Adenosine Triphosphate↗

PubMed2002

Comparison of the peak exercise response measured by the ramp and 1-min step cycle exercise protocols in patients with exertional dyspnea.

STUDY OBJECTIVES: To compare the peak exercise response and determine the limits of agreement between the ramp and the 1-min step cycle protocols in a representative population of patients with exertional breathlessness attending a respiratory outpatient clinic. DESIGN: Crossover with the test order double blinded and randomized. SETTING: Outpatient exercise physiology laboratory. PATIENTS: Twenty-two patients (12 men; mean [SD] age, 59 [8] years; FEV(1), 71% [21%]) with lung disease and/or exertional breathlessness. INTERVENTION: Symptom-limited, maximum cycle exercise tests using a ramp and a 1-min step work rate (WR) protocols. The two protocols were assigned to subjects in a randomized manner. MEASUREMENTS AND RESULTS: Oxygen uptake (O(2)), minute ventilation (E), heart rate (HR), WR, exercise time, and Borg scores were compared at symptom-limited peak exercise. The mean (SD) peak values for the ramp and the step protocols, respectively, were as follows: peak O(2), 1.51 (0.44) L/min and 1.49 (0.43) L/min; peak E, 50.8 (12.9) L/min and 49.9 (14.5) L/min; and peak HR, 133 (24) beats/min and 131 (22) beats/min (p > 0.05). There were no significant differences between breathlessness and perceived exertion at peak exercise. Peak WR (WRpeak) and exercise time were significantly higher using the ramp protocol: 110.5 (37.1) W vs 105.6 (35.6) W, and 8.2 (2.0) min vs. 7.6 (1.9) min, respectively. CONCLUSIONS: The ramp protocol leads to a higher WRpeak, and this may have implications for exercise prescription. However, there were no significant differences between the two protocols for the peak physiologic responses. The choice of protocol for the measurement of maximal exercise capacity remains one of laboratory preference.

Aged↗