Hypercholesterolemia increases mitochondrial oxidative stress and enhances the MPT response in the porcine myocardium: beneficial effects of chronic exercise.

Hypercholesterolemia has been suggested to have direct negative effects on myocardial function due to increased reactive oxygen species (ROS) generation and increased myocyte death. Mitochondrial permeability transition (MPT) is a significant mediator of cell death, which is enhanced by ROS generation and attenuated by exercise training. The purpose of this study was to investigate the effect of hypercholesterolemia on the MPT response of cardiac mitochondria. We tested the hypothesis that familial hypercholesterolemic (FH) pigs would have an enhanced MPT response and that exercise training could reverse this phenotype. MPT was assessed by mitochondrial swelling in response to 10-100 µM Ca(2+). FH pigs did show an increased MPT response to Ca(2+) that was associated with decreases in the expression of the putative MPT pore components mitochondrial phosphate carrier (PiC) and cyclophilin-D (CypD). FH also caused increased oxidative stress, depicted by increased protein nitrotyrosylation, as well as decreased levels of reduced GSH in cardiac mitochondria. Expression of the mitochondrial antioxidant enzymes manganese superoxide dismutase (MnSOD), thioredoxin-2 (Trx2), and peroxiredoxin-3 (Prx3) was greatly reduced in the FH pigs. In contrast, cytosolic catalase expression and activity were increased. However, chronic exercise training was able to normalize the MPT response in FH pigs, reduce mitochondrial oxidative stress, and return MnSOD, Trx2, Prx3, and catalase expression/activities to normal. We conclude that FH reduces mitochondrial antioxidants, increases mitochondrial oxidative stress, and enhances the MPT response in the porcine myocardium, and that exercise training can reverse these detrimental alterations.

Diseases associated with photosensitivity.

Photosensitive disorders may be classified as those entirely caused by solar exposure and the photoaggravated disorders. Those in the former category include polymorphic light eruption, juvenile spring eruption, actinic prurigo, hydroa vacciniforme, solar urticaria, also chronic actinic dermatitis. Genodermatoses whose expression mainly depends on UV or light exposure include the DNA repair deficient disorders, some disorders of cornification, the Smith-Lemli-Opitz syndrome and porphyria. Examples of photoaggravated diseases include lupus erythematosus, erythema multiforme, atopic eczema, psoriasis, viral exanthemata, pemphigus, dermatitis herpetiformis and rosacea. Drugs and chemicals may interact with UV to induce photosensitivity. In many of these diseases the action spectrum is known or may be determined by phototesting. Recognition of the reaction patterns associated with the photodermatoses greatly assists clinical classification of the photodermatoses.

Factors influencing the photo-reproduction of hydroa vacciniforme lesions.

Hydroa vacciniforme vesicles can be reproduced experimentally with repetitive UVA irradiations, but this photo-reproduction is not constant. The aim of this study was to search for the factors that influence photo-reproduction. To reproduce hydroa vacciniforme lesions six patients underwent repetitive UVA and polychromatic irradiations on the back. In four patients out of six, UVA irradiation with high doses induced papulo-vesicular lesions. Photo-induced lesions were very close to those induced by sunlight. Photo-reproduction failed when phototesting was done after or shortly before remission. Therefore, the absence of photo-reproduction appears to be a good prognostic factor.

[Hydroa vacciniforme - action spectrum. UV - tolerance following photochemotherapy]. / Hydroa vacciniforme - Aktionsspektrum. UV-Toleranz nach Photochemotherapie.

In a 14-year-old boy with hydroa vacciniforme by UV-testing was found to be the provoking wave band region. Tolerance to artificial UV-and sunlight was achieved by inducing pigmentation with oral methoxsalen photochemotherapy (PUVA).