Secretion of salivary statherin is compromised in uncontrolled diabetic patients.

Background: Statherin is an important salivary protein for maintaining oral health. The purpose of the current study was to determine if differences in statherin levels exist between diabetic and healthy subjects.

Methods: A total of 48 diabetic and healthy controls were randomly selected from a community-based database.

Silk fibroin scaffolds promote formation of the ex vivo niche for salivary gland epithelial cell growth, matrix formation, and retention of differentiated function.

Salivary gland hypofunction often results from a number of causes, including the use of various medications, radiation for head and neck tumors, autoimmune diseases, diabetes, and aging. Since treatments for this condition are lacking and adult salivary glands have little regenerative capacity, there is a need for cell-based therapies to restore salivary gland function. Development of these treatment strategies requires the establishment of a system that is capable of replicating the salivary gland cell "niche" to support the proliferation and differentiation of salivary gland progenitor cells.

A melatonin-based fluorescence method for the measurement of mitochondrial complex III function in intact cells.

Mitochondrial complex III (MC-3) plays a pivotal role in electron transfer and oxidative phosphorylation. Impaired MC-3 functions may contribute to a variety of diseases by interrupting normal bioenergetics and increasing reactive oxygen production and oxidative stress. Currently, MC-3 function is assessed by measuring the cytochrome c reductase activity spectrophotometrically in isolated mitochondria or MC-3.

Role of β-adrenergic receptors in regulation of hepatic fat accumulation during aging.

Excessive fat accumulation in liver (hepatic steatosis) predisposes to hepatic functional and structural impairment and overall metabolic risk. Previous studies noted an association between hepatic steatosis and age in humans and rodents. However, the mechanisms leading to age-associated hepatic fat accumulation remain unknown.

Geldanamycin derivative ameliorates high fat diet-induced renal failure in diabetes.

Diabetic nephropathy is a serious complication of longstanding diabetes and its pathogenesis remains unclear. Oxidative stress may play a critical role in the pathogenesis and progression of diabetic nephropathy. Our previous studies have demonstrated that polyunsaturated fatty acids (PUFA) induce peroxynitrite generation in primary human kidney mesangial cells and heat shock protein 90β1 (hsp90β1) is indispensable for the PUFA action.

Impaired mitochondrial complex III and melatonin responsive reactive oxygen species generation in kidney mitochondria of db/db mice.

We have previously demonstrated that melatonin, at pharmacological concentrations, causes rapid reactive oxygen species (ROS) generation at the antimycin-A sensitive site of mitochondrial complex III (MC-3). In the current work, we used this melatonin response to investigate the role of mitochondrial dysfunction in the development of diabetic nephropathy. We find that the development of diabetic nephropathy, as indicated by hyperfiltration and histopathological lesions in the kidney of db/db mice, is associated with diminished melatonin-induced ROS generation and MC-3 activity, indicating impaired MC-3 at the antimycin-A site.

The role of mitochondrial complex III in melatonin-induced ROS production in cultured mesangial cells.

Melatonin is a potent scavenger of reactive oxygen (ROS) and reactive nitrogen species (RNS). At pharmacological concentrations, however, melatonin is documented to cause ROS/RNS production, especially in cultured cancerous cells. Currently, the mechanism responsible for melatonin-induced ROS generation remains elusive.

Loss of manganese superoxide dismutase leads to abnormal growth and signal transduction in mouse embryonic fibroblasts.

Manganese superoxide dismutase (MnSOD) in the mitochondria plays an important role in cellular defense against oxidative damage. Homozygous MnSOD knockout (Sod2(-/-)) mice are neonatal lethal, indicating the essential role of MnSOD in early development. To investigate the potential cellular abnormalities underlying the aborted development of Sod2(-/-) mice, we examined the growth of isolated mouse embryonic fibroblasts (MEFs) from Sod2(-/-) mice.

Linoleic acid-induced mitochondrial Ca(2+) efflux causes peroxynitrite generation and protein nitrotyrosylation.

It is well known that excessive non-esterified fatty acids in diabetes contribute to the pathogenesis of renal complications although the mechanism remains elusive. Enhanced oxidative stress has been hypothesized as a unified factor contributing to diabetic complications and increased protein nitrotyrosylation has been reported in the kidneys of diabetic patients. In the current manuscript we described that linoleic acid (LA) caused mitochondrial Ca(2+) efflux and peroxynitrite production, along with increased nitrotyrosine levels of cellular proteins in primary human mesangial cells.

Distinct pathways of ERK activation by the muscarinic agonists pilocarpine and carbachol in a human salivary cell line.

Cholinergic-muscarinic receptor agonists are used to alleviate mouth dryness, although the cellular signals mediating the actions of these agents on salivary glands have not been identified. We examined the activation of ERK1/2 by two muscarinic agonists, pilocarpine and carbachol, in a human salivary cell line (HSY). Immunoblot analysis revealed that both agonists induced transient activation of ERK1/2.

Heat shock protein 90beta1 is essential for polyunsaturated fatty acid-induced mitochondrial Ca2+ efflux.

Nonesterified fatty acids may influence mitochondrial function by alterations in gene expression, metabolism, and/or mitochondrial Ca(2+) ([Ca(2+)](m)) homeostasis. We have previously reported that polyunsaturated fatty acids induce Ca(2+) efflux from mitochondria, an action that may deplete [Ca(2+)](m) and thus contribute to nonesterified fatty acid-responsive mitochondrial dysfunction. Here we show that the chaperone protein heat shock protein 90 beta1 (hsp90beta1) is required for polyunsaturated fatty acid-induced mitochondrial Ca(2+) efflux (PIMCE).

Regulation of STIM1, store-operated Ca2+ influx, and nitric oxide generation by retinoic acid in rat mesangial cells.

It has been shown that store-operated Ca(2+) influx (SOC) plays critical roles in the activation of endothelial nitric oxide (NO) synthase (eNOS) and generation of NO in endothelial cells. Recent studies indicate stromal interaction molecule 1 (STIM1) is the molecule responsible for SOC activation following Ca(2+) depletion in the ER. Retinoic acids (RA) have beneficial effects in the treatment of renal diseases.

Inhibition of CD95-mediated apoptosis through beta 1 integrin in the HSG epithelial cell line.

The HSG cell line serves as a model for salivary gland epithelial progenitor cell differentiation. In order for a progenitor cell to differentiate, the cell must maintain viability within its niche. Studies were designed to elucidate the mechanism for integrin-mediated HSG cell survival.

Polyunsaturated fatty acids mobilize intracellular Ca2+ in NT2 human teratocarcinoma cells by causing release of Ca2+ from mitochondria.

In a variety of disorders, overaccumulation of lipid in nonadipose tissues, including the heart, skeletal muscle, kidney, and liver, is associated with deterioration of normal organ function, and is accompanied by excessive plasma and cellular levels of free fatty acids (FA). Increased concentrations of FA may lead to defects in mitochondrial function found in diverse diseases. One of the most important regulators of mitochondrial function is mitochondrial Ca(2+) ([Ca(2+)](m)), which fluctuates in coordination with intracellular Ca(2+) ([Ca(2+)](i)).

Differential regulation of intracellular calcium oscillations by mitochondria and gap junctions.

Fluctuations of intracellular Ca2+ ([Ca2+]i) regulate a variety of cellular functions. The classical Ca2+ transport pathways in the endoplasmic reticulum (ER) and plasma membrane are essential to [Ca2+]i oscillations. Although mitochondria have recently been shown to absorb and release Ca2+ during G protein-coupled receptor (GPCR) activation, the role of mitochondria in [Ca2+]i oscillations remains to be elucidated.

beta-Adrenergic-responsive activation of extracellular signal-regulated protein kinases in salivary cells: role of epidermal growth factor receptor and cAMP.

The beta-adrenergic receptor agonist isoproterenol exerts growth-promoting effects on salivary glands. In this study, activation of ERKs, members of the mitogen-activated protein kinase family, by isoproterenol was examined in a human salivary gland cell line (HSY). Immunoblot analysis indicated that isoproterenol (10(-5) M) induced transient activation of ERK1/2 (4.

Involvement of calcineurin in transforming growth factor-beta-mediated regulation of extracellular matrix accumulation.

Calcineurin is a calcium-dependent, serine/threonine phosphatase that functions as a signaling intermediate. In this study, we investigated the role of calcineurin in transforming growth factor-beta (TGF-beta)-mediated cellular effects and examined the signaling pathway involved in activation of calcineurin. Calcineurin is activated by TGF-beta in a time- and dose-dependent manner.

Epidermal growth factor upregulates beta-adrenergic receptor signaling in a human salivary cell line.

The effects of epidermal growth factor (EGF) on the beta-adrenergic receptor-coupled adenylyl cyclase system were studied in a human salivary cell line (HSY). The beta-adrenergic agonist isoproterenol (10(-5) M) stimulated adenylyl cyclase activity by approximately 2-fold, and the isoproterenol response was increased 1.8-fold after prolonged (48 h) exposure to EGF (5 x 10(-10) M).

Epidermal growth factor-induced depletion of the intracellular Ca2+ store fails to activate capacitative Ca2+ entry in a human salivary cell line.

Epidermal growth factor (EGF) is a multifunctional factor known to influence proliferation and function of a variety of cells. The actions of EGF are mediated by EGF receptor tyrosine kinase pathways, including stimulation of phospholipase Cgamma and mobilization of intracellular Ca(2+) ([Ca(2+)](i)). Generally, agonist-mediated Ca(2+) mobilization involves both Ca(2+) release from internal stores and Ca(2+) influx activated by store depletion (i.

Extracellular Adenosine Triphosphate Triggers Arrhythmias and Elemental Redistribution in Electrically Stimulated Rat Cardiac Myocytes.

An increase in extracellular adenosine triphosphate (ATP) is arrhythmogenic in rat cardiac myocytes and extracellular ATP levels are elevated during cardiac ischemia. To gain insight into the mechanism by which the arrhythmic contractions are generated, we investigated changes in subcellular elemental content by electron probe microanalysis (EPMA) in isolated adult rat cardiac myocytes stimulated by the ATP analog, 2-methylthio-ATP (2-M-S-ATP). We also measured the effects of 2-M-S-ATP stimulation on myocyte cell shortening.