Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of studies have found that increasing lead exposure is associated with increases in blood pressure in humans. Studies with animals suggest that lead-induced increases in vascular resistance account for these increases in blood pressure. The present study assessed cardiovascular functioning at rest and in response to acute stress for 9(1/2) year old children (N=122) having relatively low prenatal (cord) blood lead levels (M=1.98 microg/dL, SD=1.75) and low postnatal (early childhood) blood lead levels (M=4.62 microg/dL, SD=2.51). Higher cord blood levels were associated with higher baseline systolic blood pressure (SBP), and higher early childhood lead levels were associated with greater total peripheral (vascular) resistance (TPR) responses to acute stress. In addition, a negative association between blood lead levels and stroke volume (SV) suggests that lead-induced increases in vascular resistance were sufficient to produce cardiac afterload, a situation arising when blood pressure in the aorta makes it difficult for the left ventricle to eject blood. These effects were not mediated by differences in task performance or emotional responses to the acute stress tasks. Finally, these effects were significant for lead levels considered low, notably, below the 10 microg/dL threshold currently adopted by the CDC for deleterious effects.
 ...
PMID:Prenatal and early childhood blood lead levels and cardiovascular functioning in 9(1/2) year old children. 1591 79

E3 ligases are essential scaffold proteins, facilitating the transfer of ubiquitin from E2 enzymes to lysine residues of client proteins via isopeptide bonds. The specificity of substrate binding and the expression and localization of E3 ligases can, however, endow these proteins with unique features with variable effects on mitochondrial, metabolic and CNS function. By comparing and contrasting two E3 ligases, Parkin and C-terminus of HSC70-Interacting protein (CHIP) we seek to highlight the biophysical properties that may promote mitochondrial dysfunction, acute stress signaling and critical developmental periods to cease in response to mutations in these genes. Encoded by over 600 human genes, RING-finger proteins are the largest class of E3 ligases. Parkin contains three RING finger domains, with R1 and R2 separated by an in-between region (IBR) domain. Loss-of-function mutations in Parkin were identified in patients with early onset Parkinson's disease. CHIP is a member of the Ubox family of E3 ligases. It contains an N-terminal TPR domain and forms unique asymmetric homodimers. While CHIP can substitute for mutated Parkin and enhance survival, CHIP also has unique functions. The differences between these proteins are underscored by the observation that unlike Parkin-deficient animals, CHIP-null animals age prematurely and have significantly impaired motor function. These properties make these E3 ligases appealing targets for clinical intervention. In this work, we discuss how biophysical and metabolic properties of these E3 ligases have driven rapid progress in identifying roles for E3 ligases in development, proteostasis, mitochondrial biology, and cell health, as well as new data about how these proteins alter the CNS proteome.
 ...
PMID:Alterations in the E3 ligases Parkin and CHIP result in unique metabolic signaling defects and mitochondrial quality control issues. 2885 15