Depletion of Tip60/Kat5 affects the hepatic antioxidant system in mice

Tat-interactive protein 60 kDa (TIP60, also known as lysine acetyltransferase 5 [KAT5]) is a member of the MYST protein family with histone acetyltransferase activity. Recent studies have reported that TIP60 has multiple functions in many signal transduction mechanisms, especially p53-mediated apoptosis. Although the activation of apoptosis signaling pathways requires the presence of cellular reactive oxygen species (ROS) at a certain level, an imbalance between the production and consumption of ROS in cells results in oxidative stress (OS). In this study, we investigated for the first time how the absence of the Tip60 gene in the liver affects gene expression, enzyme activity, and protein expression of the hepatic antioxidant members localized in the cytoplasm, including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST). First, we successfully generated liver-specific Tip60 knockout mice (mutants) using Cre/LoxP recombination. The reduced glutathione level and nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) expression, a marker of OS, increased significantly in the Tip60 mutant liver. Gene expression, activity, and protein expression of the enzymatic antioxidant system, including SOD, CAT, GR, GPx, and GST were investigated in mutants and control groups. Despite a significant correlation between the gene, enzyme activity, and protein content for CAT and GR, this was not true for SOD and GPx. The overall results suggest that TIP60 acts on the hepatic antioxidant system both at the gene and protein levels, but the actual effect of the deletion of Tip60 is observed at the protein level, especially for SOD and GPx.     

Elevated levels of matrix metalloprotein-3 in patients with coronary aneurysm: A case control study

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of arterial aneurysms through increased proteolysis of extracellular matrix proteins. Increased proteolysis due to elevated matrix degrading enzyme activity in the arterial wall may act as a susceptibility factor for the development of coronary aneurysms. The aim of this study was to investigate the association between MMPs and presence of coronary aneurysms. METHODS: Thirty patients with aneurysmal coronary artery disease and stable angina were enrolled into study (Group 1). Fourteen coronary artery disease patients with stable angina were selected as control group (Group 2). MMP-1, MMP-3 and C-reactive protein (CRP) were measured in peripheral venous blood and matched between the groups. RESULTS: Serum MMP-3 level was higher in patients with aneurismal coronary artery disease compared to the control group (20.23 +/- 14.68 vs 11.45 +/- 6.55 ng/ml, p = 0.039). Serum MMP-1 (13.63 +/- 7.73 vs 12.15 +/- 6.27 ng/ml, p = 0.52) and CRP levels (4.78 +/- 1.47 vs 4.05 +/- 1.53 mg/l, p = 0.13) were not significantly different between the groups. CONCLUSION: MMPs can cause arterial wall destruction. MMP-3 may play role in the pathogenesis of coronary aneurysm development through increased proteolysis of extracellular matrix proteins.     

Ultrastructural Changes in the Kidney of Rats with Acute Exposure to Cadmium and Effects of Exogenous Metallothionein

Ultrastructural changes in the kidneys of rats after acute cadmium exposure and the effects of exogenous metallothionein (MT) were studied by transmission electron microscopy. Thirty-six adult Wistar rats were divided into three groups. Cadmium chloride (CdCl₂) (3.5 mg/kg/day) was injected subcutaneously in the first group. In the second group, 30 μmol/kg MT was administered in addition to CdCl₂. Control rats received 0.5 ml subcutaneous saline solution. Four rats from each group were killed on days 1, 3, 5, and 7 after administration of the compounds. Kidney tissues were taken and fixed in 2.5% glutaraldehyde solution for electron microscopic observations. Tissue damage in kidney increased as time passed since the administration of CdCl₂ in the first group. Degeneration in the proximal and distal tubules was observed. Increased apoptosis was seen in the proximal tubules epithelium, especially on day 7. Peritubular capillaries became dilated, there was degeneration of the endothelial cells, and the amount of intertubular collagen fibers was increased. On day 1, irregular microvilli in the proximal tubules, deepening of the basal striations, and myelin figures; on day 3, multiple vesicular mitochondria and regions of edema around tubules; on days 5 and 7, increased apoptotic cell in the proximal tubules and widened rough endoplasmic reticulum of the endothelial cells of glomerular capillaries were observed. We observed that the structural alterations that increased depending on the day of Cd administration decreased after exogenous MT administration, the dilation of the peritubular capillaries persisted, and there were degenerated proximal tubules. It was established that cadmium chloride was toxic for kidney cortex and caused structural damage. Exogenous MT partly prevents CdCl₂-induced damage.     

May primary empty sella turcica be a cause of isolated ACTH deficiency? A case report and the review of related literature

Isolated ACTH deficiency is an uncommon cause of secondary adrenocortical insufficiency and accompaniment with primary empty sella has been reported in several cases. We present a case of isolated ACTH deficiency associated with empty sella. A sixty-two year old woman was admitted to our endocrine clinic with complaints of weakness, fatigue, weight loss, nausea, vomiting, and lack of appetite for about one month. Physical examination indicated orthostatic hypotension and epigastric tenderness. Laboratory investigations revealed hypoglycemia, hyponatremia and anemia, in addition low plasma cortisole and ACTH levels. Serum cortisole responses to short and prolonged ACTH stimulation were tested and partial and accurate responses were obtained, respectively. Plasma ACTH and serum cortisole levels failed to respond after intravenous injection of human corticotropin releasing hormone. Other hypophysial hormone levels were within the normal reference ranges. Although cranial and abdominal computerized tomography images were evaluated as normal, cranial magnetic resonance imaging of the pituitary gland revealed 'primary empty sella turcica'. Replacement therapy with methylprednisolon resulted in the improvement of hypoglycemia, hyponatremia and clinical symptoms. Based on these results, the patient was diagnosed as isolated ACTH deficiency and was scheduled for follow up by our outpatient clinic. Our report is consistent with other reports pointing out that primary empty sella may be responsible for pathogenesis of isolated ACTH deficiency.