Nitric oxide (NO) can trigger either necrotic or apoptotic cell death. We have used PC12 cells to investigate the extent to which NO-induced cell death is mediated by mitochondria. Addition of NO donors, 1 mM S-nitroso-N-acetyl-DL-penicillamine (SNAP) or 1 mM diethylenetriamine-NO adduct (NOC-18), to PC12 cells resulted in a steady-state level of 1-3 microM: NO, rapid and almost complete inhibi...

In this research, we investigated the cytotoxic mechanisms of Cochlodinium polykrikoidescell lysate on isolated rat liver hepatocytes.This micro algae is responsible for a severe and widespread harmful algal bloom in the Persian Gulf and Gulf of Oman (2008-2009). Isolated hepatocytes were obtained by collagenase perfusion of Sprague-Dawley rat liver.According to our results, incubation of algal...

Objective(s):Several investigations have revealed that caspase-14 is responsible for the epidermal differentiation and cornification, as well as the regulation of moisturizing effect. However, the precise regulation mechanism is still not clear. This study was aimed to investigate the expression of caspase-14 in filaggrin-deficient normal human epidermal keratinocytes (NHEKs) and to explore the...

Prior heat stress (HS) or the selective overexpression of hsp72 prevents apoptosis caused by exposure to metabolic inhibitors by protecting the mitochondrial membrane and partially reducing caspase-3 activation. Focal adhesion kinase (FAK), a tyrosine kinase, exhibits anti-apoptotic properties and is a potential target for degradation by caspase-3. This study tested the hypothesis that hsp72 in...

RATIONALE Endothelial injury is an initial mechanism mediating cardiovascular disease. OBJECTIVE Here, we investigated the effect of hyperhomocysteinemia on programed cell death in endothelial cells (EC). METHODS AND RESULTS We established a novel flow-cytometric gating method to define pyrotosis (Annexin V(-)/Propidium iodide(+)). In cultured human EC, we found that: (1) homocysteine and l...

Parkinson's disease is characterized by a loss of dopaminergic nigrostriatal neurons. This neuronal loss is mimicked by the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). MPP+ toxicity is mediated through inhibition of mitochondrial complex I, decreasing ATP production, and upregulation of oxygen radicals. There is evidence that the cell death induced by MPP+ is apoptotic and that inhibition of...

Cocaine induces apoptosis in fetal rat myocardial cells (FRMCs). However, the mechanisms are not clear. The present study examined the role of p38 mitogen-activated protein kinase (MAPK) and cytochrome c release in the cocaine-induced apoptosis in primary culture of FRMCs prepared from the fetal heart of gestational age of 21 days. Cocaine induced time-dependent, concurrent increases in cytochr...

Synthetic caspase inhibitors and particularly broad-spectrum caspase inhibitors can prevent cells from death or at least slow down cell death process and abrogate some apoptotic hallmarks [Kitanaka, C., Kuchino, Y., 1999. Caspase-independent programmed cell death with necrotic morphology. Cell Death and Differentiation 6, 508-515]. However, not all synthetic caspase inhibitors diminish cell dea...

Biochemical studies suggest that caspase activity is required for a functional mitotic checkpoint (MC) and mitotic slippage. To test this directly, we followed nontransformed human telomerase immortalized human retinal pigment epithelia (RPE-1) cells through mitosis after inhibiting or depleting selected caspases. We found that inhibiting caspases individually, in combination, or in toto did no...