Mutations in the ␣-synuclein and parkin genes cause heritable forms of Parkinson's disease. In the present study, we examined the possible functional relationship between the parkin and ␣-synuclein genes in a conditionally immortalized embryonic hippocampal cell (H19-7) line. Whereas transient transfection of ␣-synuclein into neuronal H19-7 cells caused the formation of its intracytoplasmic inclusions and a significant cell death, the combined overexpression of parkin restored the ␣-synucleininduced decrease in cell viability to control levels. In addition, the overexpression of parkin was found to generate selective cleavage of ␣-synuclein. Furthermore, the cytoprotective effect of parkin on ␣-synuclein-induced cell death was not inhibited in the presence of a proteasome inhibitor. Interestingly, the overexpression of parkin induced the activation of an intracellular cysteine protease, calpain, but not caspase, and the cytoprotective effect of parkin on ␣-synuclein cytotoxicity was significantly inhibited by the presence of calpain-specific inhibitors. In conclusion, our results suggest that parkin accelerates the degradation of ␣-synuclein via the activation of the nonproteasomal protease, calpain, leading to the prevention of ␣-synuclein-induced cell death in embryonic hippocampal progenitor cells.
PurposeTesticular microlithiasis (TM) is an uncommon pathologic condition that is commonly diagnosed by scrotal ultrasonography. Indirect evidence suggests that this syndrome may be associated with an increased risk of testicular malignancy and infertility.Materials and MethodsA total of 1,439 patients undergoing scrotal ultrasound during a 6-year, 5-month period (January 2003 to May 2009) were retrospectively reviewed. Any possible association of TM with pathologic findings was assessed. Among patients with TM, further grading of TM with testicular cancer and semen analysis of the infertile group with TM were also performed.ResultsTM was diagnosed in 87 patients (6.0%) out of a total of 1,439. Of all established pathologic entities, only testicular malignancy and infertility were meaningfully associated with TM. There was no significant difference in the prevalence of testicular cancer between each grade. Seminal profiles (sperm count, motility, morphology, and white blood cell count) were not found to be statistically different between infertile men with and without TM.ConclusionsThe prevalence of TM in symptomatic men was found to be 6.0% with significant co-occurrence of TM, testicular cancer, and infertility. Further grading of TM does not seem to be essential with regard to the detection of patients with testicular cancer and TM. TM showed no significant effect on the seminal profiles of infertile men.
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