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Objectives: The incidence of Parkinson's disease (PD) is increasing as the global population ages. 6- hydroxydopamine (6-OHDA) can induce PD-like neuropathology and biochemical changes in both in vitro and in vivo models. Therefore, clarification of the molecular mechanism of 6-OHDA-induced cell death might contribute to the understanding of the pathogenesis of PD. Methods: With this goal in mind, we investigated the role of protein kinase C delta (PKC delta) in 6-OHDAdependent death using the pheochromocytoma cell line, PC12. Cells were treated with 6-OHDA to induce toxicity with or without pretreatment using rottlerin (a PKC delta inhibitor), bisindolylmaleimide I (a general PKC inhibitor), Gö6976 (a PKC inhibitor selective for calcium-dependent PKC isoforms), or phorbol-12- myristate-13-acetate (PMA, a PKC activator). Results: Phorbol-12-myristate-13-acetate decreased cell survival and increased the rate of apoptosis while rottlerin increased cell survival and decreased the rate of apoptosis. In contrast, neither bisindolylmaleimide I nor Go¨6976 affected 6-OHDA-induced cell death. Western analysis demonstrated that phosphorylation of PKC delta on Thr 505 as well as extracellular signal-regulated kinase (ERK) phosphorylation increased after exposure to 6-OHDA. This increase in PKC delta phosphorylation was potentiated by PMA. However, rottlerin attenuated the 6-OHDA-stimulated increase in PKC delta and ERK phosphorylation. Conclusion: These data suggest that PKC delta, rather than classic-type PKC (alpha, beta1, beta2, gamma), participates in 6-OHDA-induced neurotoxicity in PC12 cells, and PKC delta activity is required for subsequent ERK activation during cell death. [ABSTRACT FROM AUTHOR]

The brachial-ankle pulse wave velocity (baPWV) is a useful index of arterial stiffness. Mean platelet volume (MPV), an indicator of platelet activation, is associated with hypertension, stroke, and coronary artery disease, all of which may be caused by arteriosclerosis. However, little research has been conducted to investigate the relationship between MPV and arterial stiffness. In this cross-sectional study, we investigated the relationship between platelet count, MPV, and baPWV in 2645 apparently healthy Chinese participants (1676 men, 969 women) in a general health examination. Different metabolic parameters were compared across MPV quintiles (Q1: ≤≤8.1 fl, Q2: 8.2--8.5 fl, Q3: 8.6--9.6 fl, Q4: 9.7--10.7 fl, and Q5: ≥≥10.8 fl). Age-adjusted mean values of baPWV gradually increased with MPV quintiles (Q1 == 1124, Q2 == 1134, Q3 == 1199, Q4 == 1207, and Q5 == 1270 cm/s). Univariate analysis showed that age, sex, smoking status, body mass index (BMI), systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), total platelet count, and MPV were significantly associated with baPWV. In addition, age, sex, BMI, MPV, SBP, and FPG were significant factors in the multivariate model with baPWV. Notably, MPV was found to be a significant determinant for baPWV (ββ == 0.198; P < 0.001). The findings show that elevated MPV is positively correlated to arterial stiffness. [ABSTRACT FROM AUTHOR]