306 Subject Synaptosomes

The —33 kDa band (32-34 kDa) is close in molecular mass to dysbindin-1C, which lacks the NTR of dysbindin-1 A but is otherwise identical to dysbindin-1 A (see Section 2.2.2.2.1). It is consequently difficult to determine if the —33 kDa band represents (1) dysbindin-lC itself, (2) a degradative product of dysbindin-1 A missing the NTR, or (c) some combination of the first two possibilities. The first possibility seems most likely, however, because the —33 kDa band is absent in some tissues (e.g., cerebellum, kidney, and liver) where the —50 kDa band (i.e., dysbindin-1 A) is present and hence subject to degradation ( Figure 2.2-12c). Moreover, the —33 kDa band is often stronger than the 50 kDa band even in fresh tissue. We thus believe that the —33 kDa band does represent dysbindin-1C. It is seen in the heart, lung, skeletal muscle, striatum, hippocampal formation, and cerebral cortex (e.g., O Figure 2.2-12a and c). In synaptosomes of the mouse and human brain, the —33 kDa isoform is concentrated in synaptic vesicle and PSD fractions with very little, if any, present in the presynaptic membrane fraction (Talbot et al., in preparation). 

Fatemi SH, Earle JA, Stary JM, Lee S, Sedgewick J. 2001. Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia. Neuroreport 12 3257-3262. 

Keller JN, Mark RJ, Bruce AJ, Blanc E, Rothstein JD, Uchida K, Waeg G, Mattson MP (1997) 4-Hydroxynonenal, an aldehydic product of membrane Upid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience 80 685-696 Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, Markesbery WR (2005) Evidence of increased oxidative damage in subjects with nuld cognitive impairment. Neurology 64 1152-1156... 

GuTifiRREZ-MARTfN et al. (2002) simulated chronic exposure to OONO" by treatment of mt brain synaptosomes or plasma membrane vesicles with repetitive pulses of OONO" during at most 50 min, which efficiently produced nitrotyrosine formation in several membrane proteins including the Ca " -ATPase. The plasma membrane Ca -ATPase activity at near-physiological conditions (pH 7, submicromolar Ca, and millimolar Mg -ATP concentrations), which plays a major role in the control of synaptic [Ca ji, could be more than 75 % inhibited by a sustained exposure to micromolar OONO (e.g., to 100 pulses of lOjuM OONO ). This inhibition was irreversible and mostly due to decreased and to a 2-fold increase of the K0 5 for Ca stimulation and about 5-fold increase of the Km for Mg -ATP. [Ca ji increased to >400 nM when synaptosomes were subjected to this treatment. Reduced glutathione could afford only partial protection against the inhibition produced by micromolar OONO pulses. 

The role of taurine in the retina has been thoroughly reviewed elsewheref( and is the subject of several papers at this meeting It is of interest that taurine uptake into platelets from patients with retinitis pigmentosa has recently been shown to be decreased-. Platelets are considered to be useful models for synaptosomes in the central nervous system and have been much used in tudies of the uptake mechanisms of various biogenic amines. Since retinitis pigmentosa may also be found in patients with Friedreich s ataxia, it would be of interest to examine the transport and content of taurine in platelets from patients. 

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