Zoology


Endoproteolytic Processing of pro-BACE by Members of the Family of Eucaryotic, Subtilisin-Like Endoproteases. Shawn Corwin and Joseph F. Sucic, University of Michigan-Flint, Biology Department, Flint, MI 48502-1950; Kumar Sambamurti, Mayo Clinic, Department of Pharmacology, Jacksonville, FL 32224

The amylold beta peptide that accumulates in brain cells during the progression of Alzheimer's disease is derived from a precursor protein through the activity of an endoprotease called the Beta site Amyloid Precursor Protein Cleaving Enzyme, or BACE. BACE is synthesized as an inactive proprotein (pro-BACE) and thus requires endoproteolytic maturation. Members of the family of eucaryotic, subtilisin-like endoproteases that reside in the constitutive secretory pathway, which include furin, Paired Basic Amino Acid Cleaving Enzyme 4 (PACE4), Prohormone Convertase 5 (PC5), and Prohormone Convertase 7 (PC7), are prime candidates for the endoproteolytic maturation of pro-BACE. We have examined the ability of these enzymes to endoproteolytically process pro-BACE in vitro. Each of these enzymes has been expressed in an endoprotease-deficient strain of Chinese hamster ovary cells. Cell fractionation was then used to isolate membranes, containing Golgi and endoplasmic reticulum components, from these cells; the membran e fractions were used in in vitro processing reactions containing pro-BACE. Reactions containing the precursor to the blood clotting protein, von Willebrand's factor (pro-vWF) were used as controls, as pro-vWF is efficiently processed by all the enzymes used in these experiments. Results suggest that pro-BACE processing can be accomplished by multiple members of this enzyme family.

Effects of Gingko biloba Leaf Extract Egb 761 on the Reproductive Behaviors, Memory, and Histology of Aged Male Rats (Rattus norvegicus). Gary M. Lange, Department of Biology, Louis Cohen, Department of Psychology, Brian Gallagher, Department of Biology, and Jeff Caler, Department of Psychology, Saginaw Valley State University, University Center, MI 48710-0001; 517/790-4336; gmlange@svsu.edu

Extracts from the Gingko biloba plant (GBE) have been used in European clinical settings in the treatment of age-associated decline. This age-related decline may be, at least in part, due to chronic vascular insufficiency. GBE has been described as being effective in restoring or rejuvenating cerebral blood flow and blood flow in other regions of the body. An experimental GBE group was compared with a placebo group to test the effects of long-term, oral GBE treatment on a delayed matching-to-sample learning task and also on the reproductive behavior of healthy, aged, male rats. The specific extract of GBE used was Egb 761 purchased from the Tanakan Corporation (IPSEN 24, Rue Erlanger, 75781 Paris, France). No significant differences were seen between experimental and placebo groups as measured by the delayed marching-to-sample test. However, significant differences were observed between experimental and placebo groups in mounting behavior when these aged males were exposed to a receptive, intact female. Thes e results were examined in regard to possible physiological effects of Gingko biloba as identified via histological analysis.

An Examination of St. John's Wort and Prozac on Hypothalamic-Stimulation Induced Aggression. Alan Davis, Brian Piper, Karen Pomeroy, Edwin Bercaw, and John Renfrew, Northern Michigan University, Psychology Department, 1401 Presque Isle Avenue, Marquette, MI 49855-5301; 906/227-2974

Hypericum perforatum, more commonly referred to as Sr. John's wort, improves mood among populations suffering from depression. Currently available pharmaco-therapies for depression are employed in the control of aggression as well. However, many specific serotonin reuptake inhibitors and monoamine oxidase inhibitors (fluoxetine, imipramine, etc.) are limited in their application for the control of aggression because of unwanted side effects. …

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