Metabolic Preconditioning of Mammalian Cells: Mimetic Agents for Hypoxia Lack Fidelity in Promoting Phosphorylation of Pyruvate Dehydrogenase.

Metabolic preconditioning of mammalian cells: mimetic agents for hypoxia lack fidelity in promoting phosphorylation of pyruvate dehydrogenase.

Filed under: Depression Treatment

Cell Tissue Res. 2012 Nov 9;
Borcar A, Menze MA, Toner M, Hand SC

Induction of HIF-1? by oxygen limitation promotes increased phosphorylation and catalytic depression of mitochondrial pyruvate dehydrogenase (PDH) and an enhanced glycolytic poise in cells. Cobalt chloride and desferrioxamine are widely used as mimics for hypoxia because they increase the levels of HIF-1?. We evaluated the ability of these agents to elicit selected physiological responses to hypoxia as a means to metabolically precondition mammalian cells, but without the detrimental effects of hypoxia. We show that, while CoCl(2) does increase HIF-1? in a dose-dependent manner, it unexpectedly and strikingly decreases PDH phosphorylation at E1? sites 1, 2, and 3 (Ser(293), Ser(300), and Ser(232), respectively) in HepG2 cells. This same effect is also observed for site 1 in mouse NIH/3T3 fibroblasts and J774 macrophages. CoCl(2) unexpectedly decreases the mRNA expression for PDH kinase-2 in HepG2 cells, which likely explains the dephosphorylation of PDH observed. And nor does desferrioxamine promote the expected increase in PDH phosphorylation. Dimethyloxaloylglycine (a prolyl hydroxylase inhibitor) performs better in this regard, but failed to promote the stronger effects seen with hypoxia. Consequently, CoCl(2) and desferrioxamine are unreliable mimics of hypoxia for physiological events downstream of HIF-1? stabilization. Our study demonstrates that mimetic chemicals must be chosen with caution and evaluated thoroughly if bona fide cellular outcomes are to be promoted with fidelity.
HubMed – depression


Intergenerational educational mobility on general mental health and depressive symptoms in young women.

Filed under: Depression Treatment

Qual Life Res. 2012 Nov 9;
Tooth L, Mishra G

PURPOSE: To investigate how intergenerational educational mobility between women and their parents influences mental health/depressive symptoms in women. METHOD: We studied 5,619 women aged 31-36 years in 2009 from the Australian Longitudinal Study on Women’s Health. The short-form-36 Mental Component Summary Scores [MCS] measured mental health and the Centre for Epidemiologic Studies Depression Scale [CES-D] measured depressive symptoms. Multiple regression analyses, with adjustment for confounders, were used. RESULTS: Greater downward mobility from mothers (mother high to self low) [MCS regression estimate [?] -3.35; 95 % confidence interval [CI] -5.6,-1.1; CES-D ? 1.94; 95 % CI, 0.7,3.2], and greater (father high to self low MCS ?,-2.53; 95 % CI -4.8,-0.3] and moderate (father high to self intermediate MCS ? -1.71; 95 % CI -3.3,-0.1] downward mobility from fathers were associated with poorer mental health in women. Another strongly consistent influence on poor mental health was answering ‘don’t know/not applicable’ about parental education [mother-self MCS ? -1.34; 95 % CI, -2.3,-0.4; mother-self CES-D ? 0.52; 95 % CI 0.01,1.0; father-self MCS ? -1.19; 95 % CI -2.1,-0.3]. CONCLUSIONS: There are subtle differences for same and opposite-sex parent-daughter relationships on the impact of downwards intergenerational educational mobility on mental health in young women. These results suggest the effect of own educational attainment on mental health depends on the degree of disparity between self and parent. Future studies should consider ‘don’t know’ as a separate category rather than treating it as a ‘missing’ response.
HubMed – depression


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