Proximal-tubule molecular relay from early Protein diaphanous homolog 1 to late Rho-associated protein kinase 1 regulates kidney function in obesity-induced kidney damage.

The small GTPase protein RhoA has two effectors, ROCK (Rho-associated protein kinase 1) and mDIA1 (protein diaphanous homolog 1), which cooperate reciprocally. However, temporal regulation of RhoA and its effectors in obesity-induced kidney damage remains unclear. Here, we investigated the role of RhoA activation in the proximal tubules at the early and late stages of obesity-induced kidney damage.

Water-Soluble Phospholo[3,2-b]phosphole-P,P'-Dioxide-Based Fluorescent Dyes with High Photostability.

We recently reported that fluorescent dye PB430, which consisted of a 2-phenyl-substituted benzophosphole P-oxide skeleton that was reinforced by a methylene bridge, showed pronounced photostability and, thus, high utility for applications in super-resolution stimulated emission depletion (STED) microscopy. Herein, we replaced the methylene bridge with another P=O group to 1) investigate the role of the bridging moieties; and 2) further modulate the fluorescence properties of this skeleton. We synthesized a series of phospholo[3,2-b]phosphole-based dyes-trans-PO-PB430, cis-PO-PB430, and trans-PO-PB460-all of which showed sufficient water solubility.

Role of secretory phospholipase A(2) in rhythmic contraction of pulmonary arteries of rats with monocrotaline-induced pulmonary arterial hypertension.

Excessive stretching of the vascular wall in accordance with pulmonary arterial hypertension (PAH) induces a variety of pathogenic cellular events in the pulmonary arteries. We previously reported that indoxam, a selective inhibitor for secretory phospholipase A(2) (sPLA(2)), blocked the stretch-induced contraction of rabbit pulmonary arteries by inhibition of untransformed prostaglandin H(2) (PGH(2)) production. The present study was undertaken to investigate involvement of sPLA(2) and untransformed PGH(2) in the enhanced contractility of pulmonary arteries of experimental PAH in rats.

Inhibition of untransformed prostaglandin H(2) production and stretch-induced contraction of rabbit pulmonary arteries by indoxam, a selective secretory phospholipase A(2) inhibitor.

Involvement of secretory phospholipase A(2) (sPLA(2)) in the stretch-induced production of untransformed prostaglandin H(2) (PGH(2)) in the endothelium of rabbit pulmonary arteries was investigated. The stretch-induced contraction was significantly inhibited by indoxam, a selective inhibitor for sPLA(2), and NS-398, a selective inhibitor for cyclooxygenase-2 (COX-2). Indoxam inhibited the RGD-sensitive-integrin-independent production of untransformed PGH(2), but did not affect the RGD-sensitive-integrin-dependent production of thromboxane A(2) (TXA(2)).

Rho and Rho-kinase activity in adipocytes contributes to a vicious cycle in obesity that may involve mechanical stretch.

The development of obesity involves multiple mechanisms. Here, we identify adipocyte signaling through the guanosine triphosphatase Rho and its effector Rho-kinase as one such mechanism. Mice fed a high-fat diet (HFD) showed increased Rho-kinase activity in adipose tissue compared to mice fed a low-fat diet.

Involvement of cyclooxygenase-2 in synergistic effect of cyclic stretching and eicosapentaenoic acid on adipocyte differentiation.

The present study examined the combined effects of fish-oil-derived omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and cyclic stretching on the adipocyte differentiation of 3T3-L1 cells. Treatment with EPA alone did not inhibit the differentiation, although it partially suppressed the expressions of peroxisome proliferator-activated receptor (PPAR)-gamma(2) and CCAAT/enhancer-binding protein (C/EBP)alpha transcripts, which are considered to be indispensable for the determination of adipocyte differentiation. However, the differentiation was significantly reduced when EPA but not DHA was concomitantly applied with cyclic stretching.

Effects of olmesartan, an AT1 receptor antagonist, on hypoxia-induced activation of ERK1/2 and pro-inflammatory signals in the mouse lung.

The present study aimed to investigate the effects of olmesartan, an antagonist for angiotensin II receptor type 1(AT1), on the activation of extracellular signal-regulated kinases (ERK)1/2, tissue remodeling, and pro-inflammatory signals in the right ventricle and lung of mice during the early phase of hypobaric hypoxia. Phosphorylation of ERK1/2 in both tissue types in response to hypoxia peaked at 1-3 days, and declined rapidly in the right ventricle, whereas in the lung it was sustained for at least 8 days. Upregulation of angiotensinogen mRNA was observed in the hypoxic lung at 4-9 days, but not in the hypoxic right ventricle and pulmonary artery.

Passive stretching produces Akt- and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice.

Muscle contraction is accompanied by passive stretching or deformation of cells and tissues. The present study aims to clarify whether or not acute passive stretching evokes glucose transporter 4 (GLUT4) translocation and glucose uptake in skeletal muscles of mice. Passive stretching mainly induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a plasma membrane-rich fraction (F2) and accelerated glucose uptake in hindlimb muscles; whereas electrical stimulation, which mimics physical exercise in vivo, and insulin, each induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a fraction rich in plasma membrane (F2), and to one rich in transverse tubules (PF3), along with subsequent glucose uptake.

[Mechanical stretching inhibits adipocyte differentiation of 3T3-L1 cells: the molecular mechanism and pharmacological regulation].

Obesity frequently promotes a variety of cardiovascular diseases including atherosclerosis, hypertension, and type 2 diabetes. In a view of both the preventive and therapeutic aspects of the abovementioned diseases, most intensive clinical interventions have been primarily directed at decreasing excessive amounts of fat tissue by a change in the balance between intake and expenditure of energy; such changes are typically effected via daily exercise and diet control. Mechanical stimuli such as stretching and rubbing of fat tissues using gymnastic exercises or massage are believed to decrease obesity; however, there is no report concerning the direct effect of the mechanical stimulation on adipocytes.

Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of PPARgamma2.

This study investigated the effects of cyclic stretching on adipocyte differentiation of mouse preadipocyte 3T3-L1 cells. Confluent 3T3-L1 cells were treated with dexamethasone, 3-isobutyl-1-methylxanthine and insulin for 45 hours (induction period), followed by incubation with insulin for 9 additional days (maturation period). A transient burst of CCAAT/enhancer-binding protein (C/EBP) beta and C/EBPdelta at an early stage (approximately 3 hours) and a delayed induction (approximately 45 hours) of C/EBPalpha and PPARgamma(2) were sequentially provoked during the induction period.

[Mechanical stress and cerebrovascular response--resemblance to cerebral vasospasm after subarachnoid hemorrhage].

The autoregulatory mechanism, including myogenic response, so-called "Bayliss effect", is well developed in the brain circulatory area, where also, cerebral vasospasm is often encountered after subarachnoid hemorrhage. In the cerebral artery smooth muscle, protein kinases, such as Rho-associated kinase, tyrosine kinase, and protein kinase C, are activated in response to mechanical stresses, including stretch, pressure and flow. All of these kinases are also activated in due course of time after development of the vasospasm.

Endothelium-derived prostaglandin H2 evokes the stretch-induced contraction of rabbit pulmonary artery.

Stretch-induced contraction of rabbit pulmonary artery depends on endothelium-derived vasoactive prostanoids. We investigated which prostanoid(s) was responsible for the stretch-induced contraction of the artery, and whether integrin was involved in this mechanotransduction process. Stretch increased productions of untransformed prostaglandin H(2), prostaglandin E(2), prostaglandin F(2alpha), and thromboxane A(2) in the pulmonary artery with intact endothelium.

Interactive role of tyrosine kinase, protein kinase C, and Rho/Rho kinase systems in the mechanotransduction of vascular smooth muscles.

Blood vessels are always subjected to hemodynamic stresses including blood pressure and blood flow. The cerebral artery is particularly sensitive to hemodynamic stresses such as pressure and stretch, and shows contractions that are myogenic in nature; i.e.