Angiotensin II type 1a receptor loss ameliorates chronic tubulointerstitial damage after renal ischemia reperfusion.

We investigate whether suppressing the activation of the angiotensin II type 1a receptor (AT1a) can ameliorate severe chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR) using AT1a knockout homozygous (AT1a) male mice. To induce severe chronic TID after renal IR, unilateral renal ischemia was performed via clamping of the right renal pedicle in both AT1a and wild-type (AT1a) mice for 45 min. While marked renal atrophy and severe TID at 70 days postischemia was induced in the AT1a mice, such a development was not provoked in the AT1a mice.

Signaling pathways involved in adaptive responses to cell membrane disruption.

Plasma membrane disruption occurs frequently in many animal tissues. Cell membrane disruption induces not only a rapid and massive influx of Ca into the cytosol but also an efflux or release of various signaling molecules, such as ATP, from the cytosol; in turn, these signaling molecules stimulate a variety of pathways in both wounded and non-wounded neighboring cells. These signals first trigger cell membrane repair responses in the wounded cell but then induce an adaptive response, which results in faster membrane repair in the event of future wounds in both wounded and non-wounded neighboring cells.

Autocrine purinergic signaling stimulated by cell membrane disruption is involved in both cell membrane repair and adaptive response in MDCK cells.

Disruption and repair of plasma membranes is normally observed in many animal tissues. Recent studies demonstrated that wounding of Madin-Darby canine kidney cells potentiates membrane repair in cells adjacent to wounded cells via paracrine purinergic signaling. The present study demonstrated that cyclic adenosine monophosphate signaling in a wounded cell was induced by autocrine purinergic signaling, and protein kinase A potentiates membrane resealing for repeated wounds in those cells.

Cell membrane disruption stimulates cAMP and Ca signaling to potentiate cell membrane resealing in neighboring cells.

Disruption of cellular plasma membranes is a common event in many animal tissues, and the membranes are usually rapidly resealed. Moreover, repeated membrane disruptions within a single cell reseal faster than the initial wound in a protein kinase A (PKA)- and protein kinase C (PKC)-dependent manner. In addition to wounded cells, recent studies have demonstrated that wounding of Madin-Darby canine kidney (MDCK) cells potentiates membrane resealing in neighboring cells in the short-term by purinergic signaling, and in the long-term by nitric oxide/protein kinase G signaling.

Ca²⁺ influx-linked protein kinase C activity regulates the β-catenin localization, micromere induction signalling and the oral-aboral axis formation in early sea urchin embryos.

Sea urchin embryos initiate cell specifications at the 16-cell stage by forming the mesomeres, macromeres and micromeres according to the relative position of the cells in the animal-vegetal axis. The most vegetal cells, micromeres, autonomously differentiate into skeletons and induce the neighbouring macromere cells to become mesoendoderm in the β-catenin-dependent Wnt8 signalling pathway. Although the underlying molecular mechanism for this progression is largely unknown, we have previously reported that the initial events might be triggered by the Ca2+ influxes through the egg-originated L-type Ca2+ channels distributed asymmetrically along the animal-vegetal axis and through the stretch-dependent Ca2+channels expressed specifically in the micromere at the 4th cleavage.

Short-term potentiation of membrane resealing in neighboring cells is mediated by purinergic signaling.

Resealing of a disrupted plasma membrane in the micron-size range requires Ca(2+)-regulated exocytosis. When cells are wounded twice, the second membrane disruption reseals more quickly than the initial wound. This response is protein kinase C (PKC)-dependent and protein kinase A dependent in the early stages.

Cell membrane disruption stimulates NO/PKG signaling and potentiates cell membrane repair in neighboring cells.

Resealing of a disrupted plasma membrane at the micron-diameter range requires Ca(2+)-regulated exocytosis. Repeated membrane disruptions reseal more quickly than the initial wound, and this potentiation of membrane resealing persists for at least 24 hours after the initial wound. Long-term potentiation of membrane resealing requires CREB-dependent gene expression, which is activated by the PKC- and p38 MAPK-dependent pathway in a wounded cell.

Ca(2+) regulates the subcellular localization of adenomatous polyposis coli tumor suppressor protein.

Microtubule (MT) plus-end tracking proteins (+TIPs) are involved in the regulation of MT plus-end dynamics and stabilization. It was reported previously that an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) induced by disruption of the plasma membrane stimulates rearrangement of MTs [T. Togo, Disruption of the plasma membrane stimulates rearrangement of microtubules and lipid traffic toward the wound site, J.

Disruption of the plasma membrane stimulates rearrangement of microtubules and lipid traffic toward the wound site.

Resealing of a disrupted plasma membrane requires Ca(2+)-regulated exocytosis. Repeated disruptions reseal more quickly than the initial wound. This facilitated response requires both Ca(2+) and protein kinase C (PKC), and is sensitive to brefeldin A.

Long-term potentiation of wound-induced exocytosis and plasma membrane repair is dependent on cAMP-response element-mediated transcription via a protein kinase C- and p38 MAPK-dependent pathway.

Ca(2+)-regulated exocytosis is required for rapid resealing of disrupted plasma membranes. It has been previously demonstrated that repeated membrane disruptions reseal more quickly than the initial wound and that this facilitated response requires the transcription factor cAMP-response element-binding protein (CREB). This study examines the signaling pathway between membrane disruption and CREB-dependent gene expression in 3T3 fibroblasts.

GPI-anchored aminopeptidase is involved in the acrosome reaction in sperm of the mussel mytilusedulis.

The sperm of the mussel Mytilus had hydrolytic activities against substrates for aminopeptidase. Acrosome reaction (AR) was suppressed in the presence of aminopeptidase substrate, Phe-4-methylcoumaryl-7-amide (MCA), and an aminopeptidase inhibitor, bestatin. Treatment of sperm with phosphatidylinositol-specific phospholipase C (PI-PLC) released aminopeptidase activity from sperm and suppressed AR.

Nonmuscle myosin IIA and IIB have distinct functions in the exocytosis-dependent process of cell membrane repair.

Vesicle generation, recruitment, and exocytosis are essential for repairing disruptions of cell membranes. The functions of nonmuscle myosin IIA and IIB in this exocytotic process of membrane repair were studied by the antisense technique. Knockdown of myosin IIB suppressed wound-induced exocytosis and the membrane resealing process.

Long-term potentiation of exocytosis and cell membrane repair in fibroblasts.

We previously found that a microdisruption of the plasma membrane evokes Ca(2+)-regulated exocytosis near the wound site, which is essential for membrane resealing. We demonstrate herein that repeated membrane disruption reveals long-term potentiation of Ca(2+)-regulated exocytosis in 3T3 fibroblasts, which is closely correlated with faster membrane resealing rates. This potentiation of exocytosis is cAMP-dependent protein kinase A dependent in the early stages (minutes), in the intermediate term (hours) requires protein synthesis, and for long term (24 h) depends on the activation of cAMP response element-binding protein (CREB).