Biomedical subjects

S Scheff

Publications and source records attributed to S Scheff.

12 recordsLinked to original sources

PubMed2001

Tissue-specific alterations in the 6-hydroxylation of chlorzoxazone following traumatic brain injury in the rat.

Interest in the non-neuronal alterations following traumatic brain injury (TBI) has led to research evaluating hepatic metabolism following injury. Several models of injury demonstrate tissue-specific alterations in cytochrome P450 activity. This study examined tissue-specific alterations in cytochrome P450-mediated hydroxylation in the rat model of TBI. Male Sprague-Dawley rats received anesthesia alone, craniotomy, or craniotomy plus TBI. Rats were sacrificed at 24 and 48 h. Liver, kidney, and brain cortex microsomes were isolated. Total liver P450 content, 6-hydroxychlorzoxazone formation rate, and CYP2E1 protein were evaluated. In liver microsomes, spectral P450 was decreased to 86 +/- 5% (p < 0.05) of control at 24 h following injury, and 6-hydroxychlorzoxazone formation rate decreased to 74 +/- 18% of control (p < 0.05) at 48 h following injury. In kidney microsomes, 6-hydroxychlorzoxazone formation rate was increased to 154% of control (p < 0.01) 24 h following injury. 6-Hydroxychlorzoxazone formation rate was unaffected by TBI in brain cortical microsomes. The CYP2E1 inhibitor, 4-methylpyrazole, inhibited the formation of 6-hydroxychlorzoxazone in brain, kidney, and liver microsomes. These data demonstrate that tissue-specific alterations in 6-hydroxychlorzoxazone formation rate occur following TBI.

Animals↗

PubMed2000

The plasmin system is induced by and degrades amyloid-beta aggregates.

Amyloid-beta (Abeta) appears critical to Alzheimer's disease. To clarify possible mechanisms of Abeta action, we have quantified Abeta-induced gene expression in vitro by using Abeta-treated primary cortical neuronal cultures and in vivo by using mice transgenic for the Abeta precursor (AbetaP). Here, we report that aggregated, but not nonaggregated, Abeta increases the level of the mRNAs encoding tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Moreover, tPA and uPA were also upregulated in aged AbetaP overexpressing mice. Because others have reported that Abeta aggregates can substitute for fibrin aggregates in activating tPA post-translationally, the result of tPA induction by Abeta would be cleavage of plasminogen to the active protease plasmin. To gain insights into the possible actions of plasmin, we evaluated the hypotheses that tPA and plasmin may mediate Abeta in vitro toxicity or, alternatively, that plasmin activation may lead to Abeta degradation. In evaluating these conflicting hypotheses, we found that purified plasmin degrades Abeta with physiologically relevant efficiency, i.e., approximately 1/10th the rate of plasmin on fibrin. Mass spectral analyses show that plasmin cleaves Abeta at multiple sites. Electron microscopy confirms indirect assays suggesting that plasmin degrades Abeta fibrils. Moreover, exogenously added plasmin blocks Abeta neurotoxicity. In summation, we interpret these results as consistent with the possibility that the plasmin pathway is induced by aggregated Abeta, which can lead to Abeta degradation and inhibition of Abeta actions.

Amino Acid Sequence↗

PubMed1998

PACSIN, a brain protein that is upregulated upon differentiation into neuronal cells.

To identify genes that are differentially expressed during self-repair processes in mouse brain, we screened a subtracted cDNA library enriched for brain-specific clones. One of these clones, H74, detected a 4.4-kb mRNA predominantly expressed in brain and dorsal root ganglia neurons. Expression increased continuously during the lifespan and the state of differentiation, but decreased after entorhinal-cortex lesion. A full-length cDNA clone was isolated from a cerebellum cDNA library and characterized. Sequence analysis and database search revealed high sequence similarity to FAP52, a protein expressed in focal-adhesion contacts, and uncharacterized Echinococcus and Caenorhabditis elegans gene products. Furthermore, peptide sequences derived from human cDNA fragments showed up to 65% sequence identity at the amino acid level. The presence of a C-terminal src homology 3 (SH3) domain and its phosphorylation by casein kinase 2 (CK2) and protein kinase C (PKC) imply a role in signaling. Here we demonstrate that the gene encodes a phosphoprotein, referred to as PACSIN, with a restricted spatial and temporal expression pattern.

Adaptor Proteins, Signal Transducing↗

PubMed1994

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning.

Neural-cell adhesion molecules (N-CAMs) are members of the immunoglobulin superfamily mediating homo- and heterophilic cell-cell interactions. N-CAM exists in various isoforms which are generated by alternative splicing. During embryonic development, N-CAMs are expressed in derivatives of all three germ layers, whereas in the adult animal they are predominantly present in neural tissue. Processes like neurulation, axonal outgrowth, histogenesis of the retina and development of the olfactory system are correlated with the regulated expression of N-CAMs. We show here that N-CAM-deficient mice generated by gene targeting appear healthy and fertile, but adult mutants show a 10% reduction in overall brain weight and a 36% decline in size of the olfactory bulb. N-CAM deficiency coincides with almost total loss of protein-bound alpha-(2,8)-linked polysialic acid, a carbohydrate structure thought to be correlated with neural development and plasticity. The animals showed deficits in spatial learning when tested in the Morris water maze, whereas activity and motor abilities appeared normal.

Animals↗

PubMed1977

Progressive brain damage accelerates axon sprouting in the adult rat.

An entorhinal cortical lesion causes undamaged fibers in the deafferented hippocampus to sprout and form new connections within 4 to 7 days after the lesion was made. When a partial lesion of the entorhinal cortex precedes a second, more complete entorhinal lesion by a few days, the rate of axon sprouting is accelerated so that the response to the second lesion occurs within only 2 days. This priming effect is present within 4 days, lasts for a few weeks, and eventually subsides. This acceleration may explain, in part, the faster recovery and reduced deficits seen in behavioral studies that have followed serial lesion paradigms.

Acetylcholinesterase↗

PubMed1971