Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Controversy surrounds proper classification of neurodegeneration occurring acutely following neonatal hypoxia-ischemia (HI). By ultrastructural classification, in the first 24 h after neonatal hypoxia-ischemia in the 7-day-old (p7) rat, the majority of striatal cells die having both apoptotic and necrotic features. There is formation of a functional apoptosome, and activation of caspases-9 and -3 occurring simultaneously with loss of structurally intact mitochondria to 34.7+/-25% and loss of mitochondrial cytochrome c oxidase activity to 34.7+/-12.7% of control levels by 3 h after hypoxia-ischemia. There is also loss of the mitochondrial motor protein, kinesin. This combination of activation of apoptosis pathways simultaneous with significant mitochondrial dysfunction may cause incomplete packaging of nuclear and cytoplasmic contents and a hybrid of necrotic and apoptotic features. Evidence for an intermediate biochemistry of cell death including expression of the 17 kDa isoform of caspase-3 in dying neurons lacking a classic apoptotic morphology and degradation of the neuronal cytoskeletal protein spectrin by caspase-3 and calcium-activated calpains yielding 120 kDa and 145/150 kDa fragments, respectively, is also found. In summary, neonatal hypoxia-ischemia triggers apoptotic cascades, and simultaneously causes mitochondrial structural and functional failure. The presence of a "continuum" phenotype of cell death that varies on a cell-by-cell basis suggests that the phenotype of cell death is dependent on the energy available to drive the apoptotic pathways to completion.
 ...
PMID:Failure to complete apoptosis following neonatal hypoxia-ischemia manifests as "continuum" phenotype of cell death and occurs with multiple manifestations of mitochondrial dysfunction in rodent forebrain. 1796 29

The kinesin superfamily of motor proteins is known to be ATP-dependent transporters of various types of cargoes. In neurons, KIF17 is found to transport vesicles containing the N-methyl-D-aspartate receptor NR2B subunit from the cell body specifically to the dendrites. These subunits are intimately associated with glutamatergic neurotransmission as well as with learning and memory. Glutamatergic synapses are highly energy-dependent, and recently we found that the same transcription factor, nuclear respiratory factor 1 (NRF-1), co-regulates energy metabolism (via its regulation of cytochrome c oxidase and other mitochondrial enzymes) and neurochemicals of glutamatergic transmission (NR1, NR2B, GluR2, and nNOS). The present study tested our hypothesis that NRF-1 also transcriptionally regulates KIF17. By means of in silico analysis, electrophoretic mobility shift and supershift assays, in vivo chromatin immunoprecipitation assays, promoter mutations, and real-time quantitative PCR, we found that NRF-1 (but not NRF-2) functionally regulates Kif17, but not Kif1a, gene. NRF-1 binding sites on Kif17 gene are highly conserved among mice, rats, and humans. Silencing of NRF-1 with small interference RNA blocked the up-regulation of Kif17 mRNA and proteins (and of Grin1 and Grin2b) induced by KCl-mediated depolarization, whereas over-expressing NRF-1 rescued these transcripts and proteins from being suppressed by TTX. Thus, NRF-1 co-regulates oxidative enzymes that generate energy and neurochemicals that consume energy related to glutamatergic neurotransmission, such as KIF17, NR1, and NR2B, thereby ensuring that energy production matches energy utilization at the molecular and cellular levels.
 ...
PMID:The kinesin superfamily protein KIF17 is regulated by the same transcription factor (NRF-1) as its cargo NR2B in neurons. 2117 91