Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation releasing iron, carbon monoxide (CO), and biliverdin. We investigated subcellular localization of HO-1 using confocal ...laser scanning microscopy (CLSM) and the expression by Western blot in primary astroglial cells during differentiation and after exposure to glutamate (100
μM). CLSM analysis of immunostained HO-1 in cultured astroglial cells during differentiation showed an increase of fluorescence between 7 and 14 days and a decrease between 14 and 21, although HO-1 peaked at 14 days it remained at high levels. The distribution of HO-1 protein undergoes modification in the various cellular compartments. Furthermore, localization of the protein in untreated astrocytes at 7 days appeared prevalently localized in the cytosol and in the perinuclear region. In contrast, at 14 and 21 days, fluorescence detection suggests that HO-1 was present also in the nucleus, and in the nucleoli. Fluorescence intensity significantly increased in glutamate-treated astrocytes during all development stages and the protein appeared in the cytosol, in the nucleus and in the nucleoli. The involvement of AMPA/Ka receptors was studied in glutamate-treated astroglial cells at 14 days by the preincubation of the cells with GYKI 52466, a specific receptor inhibitor, of AMPA/Ka receptor demonstrating the involvement of these receptors. Western blot analysis of HO-1 confirmed the CLSM results. Our results demonstrate that changes in HO-1 protein expression and localization in primary cultured astroglial cells may be part of the underlying mechanisms involved in brain development as well as in neurodegenerative diseases.
Purpose
To investigate the relationship between intra-prostatic levels of heme oxygenase (HO), metaflammation in benign prostatic hyperplasia (BPH) tissue in patients with MetS and moderate–severe ...lower urinary tract symptoms (LUTS).
Methods
Between January 2012 and June 2013, 132 consecutive patients, who underwent transurethral resection of the prostate for moderate–severe LUTS, secondary to clinical BPH, were enrolled. Prostate samples were investigated for the presence of an inflammatory infiltrate, according to the Irani score, and for HO-1 and HO-2 levels measurements. Patients were evaluated for the presence of metabolic syndrome (MetS) defined by the International Diabetes Federation.
Results
We observed that subjects with MetS exhibited greater Irani score (3.0 vs. 2.0;
p
< 0.05), Irani grade (2.0 vs. 1.0;
p
< 0.05) and lower value of HO-1 (4.55 vs. 6.01;
p
< 0.05) and HO-2 (0.81 vs. 2.66;
p
< 0.05). HO-1 (3.91 vs. 5.67;
p
< 0.05) and HO-2 (1.06 vs. 1.37;
p
< 0.05) were significantly reduced in patients with high intra-prostatic inflammation (Irani score ≥4). At the multivariate logistic regression analysis, HO-1 reduction (OR 0.588;
p
< 0.01), waist circumference (OR 1.09;
p
< 0.01), triglycerides (OR 1.013;
p
< 0.05) and HDL (OR 0.750;
p
< 0.05) were independent predictors of high intra-prostatic inflammation. We also found that HO-1 reduction (OR 0.598;
p
< 0.01) and the presence of MetS (OR 34.846;
p
< 0.01) were associated with Irani score ≥4.
Conclusion
MetS-induced inflammation may play a key role in BPH. In detail, prostate metaflammation is inversely related to intra-prostatic HO-1 levels, serum HDL and positively with triglycerides.
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