21 research outputs found
Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis
Antipsychotic Drug Aripiprazole Protects Liver Cells from Oxidative Stress
Antipsychotics used to treat schizophrenia can cause drug-induced liver injury (DILI), according to the Roussel Uclaf Causality Assessment Method. The role of oxidative stress in triggering injury in these DILI cases is unknown. We repeatedly administrated two second-generation antipsychotics, aripiprazole and olanzapine, at laboratory alert levels to study underlying mechanisms in stress prevention upon acute oxidative stress. The drugs were administered continuously for up to 8 weeks. For this, hepatoma Fao cells, which are suitable for metabolic studies, were used, as the primary hepatocytes survive in the culture only for about 1 week. Four stress responses—the oxidative stress response, the DNA damage response and the unfolded protein responses in the endoplasmic reticulum and mitochondria—were examined in H2O2-treated cells by antioxidant enzyme activity measurements, gene expression and protein quantification. Oxidant conditions increased the activity of antioxidant enzymes and upregulated genes and proteins associated with oxidative stress response in aripiprazole-treated cells. While the genes associated with DNA damage response, Gadd45 and p21, were upregulated in both aripiprazole- and olanzapine-treated cells, only aripiprazole treatment was associated with upregulation in response to even more H2O2, which also coincided with better survival. Endoplasmic reticulum stress-induced Chop was also upregulated; however, neither endoplasmic reticulum nor mitochondrial unfolded protein response was activated. We conclude that only aripiprazole, but not olanzapine, protects liver cells against oxidative stress. This finding could be relevant for schizophrenia patients with high-oxidative-stress-risk lifestyles and needs to be validated in vivo
Knowledge management infrastructure in large and small organizations
Pregled elemenata infrastrukture za upravljanje znanjem - organizacijska kultura, organizacijska struktura, IT infrastruktura, zajedničko znanje, fizička okolina. Usporedba infrastrukture za UZ u velikim i malim organizacijama kroz primjere
Knowledge management infrastructure in large and small organizations
Pregled elemenata infrastrukture za upravljanje znanjem - organizacijska kultura, organizacijska struktura, IT infrastruktura, zajedničko znanje, fizička okolina. Usporedba infrastrukture za UZ u velikim i malim organizacijama kroz primjere
Knowledge management infrastructure in large and small organizations
Pregled elemenata infrastrukture za upravljanje znanjem - organizacijska kultura, organizacijska struktura, IT infrastruktura, zajedničko znanje, fizička okolina. Usporedba infrastrukture za UZ u velikim i malim organizacijama kroz primjere
Differential p16 expression levels in the liver, hepatocytes and hepatocellular cell lines
Background One of the most frequently deleted genes in cancer is CDKN2A encoding p16. This protein is often overexpressed in senescent cells, while its suppression can bypass the oncogene-induced senescence to enable transformation and tumorigenesis. The roles of the protein p16 are recently being expanded from the cell cycle progression regulator to the cellular regulator interacting in several different pathways. Yet data on its liver and liver cells’ expression are inconclusive. Methods The expression of the p16 gene in liver and liver cells was determined by RT-qPCR and compared to its protein amounts by western blotting. Results p16 is expressed at low levels in the liver and rat hepatocytes. Its expression varies from none to the considerable levels in the examined hepatocellular carcinoma cell lines (FaO and HepG2) and in immortalized mouse hepatocytes. Such significant expression differences of an important cellular regulator warrant the need to closely examine the differences in biochemical pathways correlated with the p16 expression when using hepatocytes and hepatoma liver models
p16 expression in the liver and liver cells
Results. p16 is expressed at low levels in the liver and rat hepatocytes. Its expression varies from none to the considerable levels in the examined hepatocellular carcinoma cell lines (FaO and HepG2) and in immortalized mouse hepatocytes. Such large expression differences of an important cellular regulator warrant the need to closely examine the differences in biochemical pathways correlated with the p16 expression when using hepatocytes and hepatoma liver models