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Nobuo Hashimoto

Publications and source records attributed to Nobuo Hashimoto.

At least 127 records · Page 7Linked to original sources
PubMed2003

Effects of the Ca++-permeable nonselective cation channel blocker LOE 908 on subarachnoid hemorrhage-induced vasospasm in the basilar artery in rabbits.

OBJECT: The Ca++ influx into vascular smooth-muscle cells (VSMCs) plays a fundamental role in the development and chronic effects of vasospasm after subarachnoid hemorrhage (SAH). The Ca++-permeable nonselective cation channels (NSCCs) are activated by several endothelium-derived constricting factors such as endothelin 1 (ET-1) and thromboxane A2. Moreover, the receptor-operated Ca++ channel blocker LOE 908 inhibits ET-1-induced extracellular Ca++ influx via NSCCs in the VSMCs of the basilar artery (BA) and the NSCC-dependent part of ET-1-induced vasoconstriction of BA rings. The purpose of the present study was to evaluate the in vivo role of LOE 908 on SAH-induced vasospasm. METHODS: Forty-two Japanese white rabbits were assigned to seven groups. Treatment groups consisted of the following: 1) control rabbits without SAH that received a cisternal injection of saline; 2) rabbits with SAH that were subjected to the intravenous administration of saline; 3 through 6) rabbits with SAH that underwent the intravenous administration of 0.01. 0.1, 1, or 10 mg/kg LOE 908, respectively; and 7) rabbits without SAH that underwent the intravenous administration of 10 mg/kg LOE 908. Autologous blood was injected into the cisterna magna. The caliber of the BA was measured on angiographic studies before and after the cisternal injection of autologous blood. The intravenous injection of LOE 908 inhibited the magnitude of an SAH-induced vasosapsm. In addition, the concentration of LOE 908 required to relax vasospasm (1 mg/kg) correlated with that required to block Ca++ influx into VSMCs. CONCLUSIONS: The Ca++ channel blocker LOE 908 may inhibit the magnitude of an SAH-induced vasospasm by blocking the influx of Ca++ through NSCCs in rabbit BAs. Blocking the NSCCs may represent a new treatment for cerebral vasospasm after SAH.

Acetamides↗
PubMed2003

Spinal intradural extramedullary cavernous angioma. Case report.

The spinal intradural extramedullary cavernous angioma is a rare clinical entity. Only 20 surgically treated cases have been reported. The authors report on an additional case in which the lesion was located in the cervical region, and they summarize its unique clinical features. Intradural extramedullary cavernous angiomas occur predominantly in males, in the lower thoracolumbar region, exhibit a relatively high association with subarachnoid hemorrhage, and mostly adhere to the nerve root or spinal cord. Because resection is possible without causing morbidity and because outcome depends on the severity of preoperative neurological dysfunction, precise diagnosis and timely treatment are mandatory.

Cervical Vertebrae↗
PubMed2003

Contrast-enhanced carotid color-coded duplex sonography for carotid stenting follow-up assessment.

Proper assessment of endovascular patency after carotid stent (CS) placement with carotid color-coded duplex sonography (CCCD) can be difficult. We investigated the usefulness of contrast-enhanced (CE) CCCD for post-CS follow-up. CCCD images could not depict the entire bloodstream in overlapped stents and in highly positioned stents. CE-CCCD images, however, did provide anatomic information almost equivalent to that of intra-arterial angiography. CE-CCCD is useful in screening for post-CS restenosis.

Aged↗
PubMed2002

"Supplementary motor area (SMA) seizure" rather than "SMA epilepsy" in optimal surgical candidates: a document of subdural mapping.

PURPOSE: To clarify the relationship between epileptogenic zone and supplementary motor area (SMA) in patients who were regarded as the optimal surgical candidates for their intractable SMA seizures. METHODS: We analyzed the epileptogenic zone at/or adjacent to the SMA in four patients with clinical SMA seizures. All four patients had noninvasive presurgical evaluations (long-term video/EEG monitoring, MRI, and neuroimaging with radioisotopes), which provided convergent results between ictal semiology and the epileptogenic area, and thus, they had chronically implanted subdural electrodes, and finally had focus resection with a follow-up period of more than 2 years. RESULTS: Three patients had lesions shown by MRI outside the SMA, and one patient had a lesion within the SMA. Interictal epileptiform discharges were seen at/or outside the SMA. Ictal EEG pattern originated from the SMA in one patient, from the high lateral frontal area in two patients, and from the precuneus in one patient. In the latter three patients, the ictal EEG pattern immediately spread to the SMA. Those ictal onset zones were consistently localized within/or just adjacent to the lesions revealed by MRI. Only one patient had SMA resection, and three had the resection of epileptogenic zone by preserving the SMA. No neurological deficits developed and good seizure control was achieved. CONCLUSION: Among surgical candidates for intractable SMA seizures, frontal cortex other than SMA or even parietal cortex can be epileptogenic, and thus, the SMA itself may not necessarily have to be resected. This notion is clinically important when selecting surgical candidates as well as when planning presurgical invasive evaluation in patients with intractable SMA seizures.

Adolescent↗
PubMed2002

Optimal conditions for in vivo induction of dopaminergic neurons from embryonic stem cells through stromal cell-derived inducing activity.

A method of inducing dopamine (DA) neurons from mouse embryonic stem (ES) cells by stromal cell-derived inducing activity (SDIA) was previously reported. When transplanted, SDIA-induced DA neurons integrate into the mouse striatum and remain positive for tyrosine hydroxylase (TH) expression. In the present study, to optimize the transplantation efficiency, we treated mouse ES cells with SDIA for various numbers of days (8-14 days). SDIA-treated ES cell colonies were isolated by papain treatment and then grafted into the 6-hydroxydopamine (6-OHDA)-lesioned mouse striatum. The ratio of the number of surviving TH-positive cells to the total number of grafted cells was highest when ES cells were treated with SDIA for 12 days before transplantation. This ratio revealed that grafting cell colonies was more efficient for obtaining TH-positive cells in vivo than grafting cell suspensions. When we grafted a cell suspension of 2 x 10(5), 2 x 10(4), or 2 x 10(3) cells into the 6-OHDA-lesioned mouse striatum, we observed only a few surviving TH-positive cells. In conclusion, inducing DA neurons from mouse ES cells by SDIA for 12 days and grafting cell colonies into mouse striatum was the most effective method for the survival of TH-positive neurons in vivo.

Animals↗
PubMed2002

Effects of Ca(2+) influx through nonselective cation channel on noradrenaline-induced mitogenic responses.

We have recently shown that noradrenaline induces extracellular Ca(2+) influx through nonselective cation channel (NSCC) in Chinese hamster ovary cells expressing alpha(1A)-adrenoceptors (CHO-alpha(1A)). Moreover, this NSCC is sensitive to (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908) and resistant to 1-[b-(3-[4-Methoxyphenyl]propoxy)-4-methoxyphenethyl]-1H-imidazole hydrochloride (SK&F 96365). In the present study, we characterized the effects of extracellular Ca(2+) influx through NSCC on noradrenaline-induced mitogenic responses and activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) of CHO-alpha(1A) using LOE 908 and SK&F 96365. Noradrenaline induced a mitogenic response in CHO-alpha(1A). LOE 908 completely inhibited the noradrenaline-induced mitogenesis, whereas SK&F 96365 did not inhibit it. The IC(50) value of LOE 908 for noradrenaline-induced mitogenesis was similar to that for the noradrenaline-induced increase in intracellular free Ca(2+) concentration ([Ca(2+)](i)). Noradrenaline stimulated ERK1/2 activity. The magnitude of noradrenaline-induced ERK1/2 activity in the absence of extracellular Ca(2+) was 40% of that in the presence of extracellular Ca(2+). LOE 908 partially (60%) inhibited the noradrenaline-induced ERK1/2 activity, whereas SK&F 96365 did not inhibit it. The IC(50) value of LOE 908 for noradrenaline-induced ERK1/2 activity was similar to that for the noradrenaline-induced increase in [Ca(2+)](i). Collectively, these results demonstrate that extracellular Ca(2+) influx through LOE 908-sensitive and SK&F 96365-resistant NSCC may be essential for noradrenaline-induced mitogenesis in CHO-alpha(1A). Moreover, the noradrenaline-induced ERK1/2 activity involves two distinct pathways, one dependent on extracellular Ca(2+) influx through NSCC, whereas the other is independent of the influx.

Acetamides↗
PubMed2002

Effects of extracellular Ca2+ influx on endothelin-1-induced intracellular mitogenic cascades in C6 glioma cells.

We have recently shown that endothelin-1 activates two types of Ca2+-permeable nonselective cation channels (NSCC-1 and NSCC-2) in C6 glioma cells. These channels can be distinguished by their sensitivity to blockers of the receptor-operated Ca2+ channel, 1-[b-(3-[4-methoxyphenyl]propoxy)-4-methoxyphenethyl]-1H-imidazole hydrochloride (SK&F 96365) and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908). NSCC-1 is sensitive to LOE 908 and resistant to SK&F 96365, whereas NSCC-2 is sensitive to both LOE 908 and SK&F 96365. Moreover, extracellular Ca2+ influx through these channels plays an essential role in endothelin-1-induced mitogenesis in C6 glioma cells. The purpose of the present study was to investigate the effects of extracellular Ca2+ influx on intracellular pathways of endothelin-1-induced mitogenic responses in C6 glioma cells. We focused on extracellular signal-regulated kinase 1 and 2 (ERK1/2) in this context. An inhibitor of mitogen-activated protein kinase, 2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4-one (PD 98059), abolished the endothelin-1-induced increase in ERK1/2 activity, but only partially suppressed the mitogenic response. ERK1/2 activation by endothelin-1 was partially suppressed in the absence of extracellular Ca2+. On the basis of the sensitivity to LOE 908 and SK&F 96365, Ca2+ influx through NSCC-1 and NSCC-2 plays an essential role in the extracellular Ca2+-dependent component of ERK1/2 activity. In contrast, Ca2+ influx through NSCC-2 is involved in the ERK1/2-independent component of endothelin-1-induced mitogenesis. These results indicate that (1) the endothelin-1-induced mitogenic response involves both ERK1/2-dependent and -independent mechanisms, (2) ERK1/2 activation by endothelin-1 involves an extracellular Ca2+ influx-dependent cascade as well as an extracellular Ca2+ influx-independent cascade, (3) because endothelin-1-induced mitogenesis is completely dependent on extracellular Ca2+ influx, extracellular Ca2+ influx also plays an important role in mitogenic pathways downstream of ERK1/2, (4) extracellular Ca2+ influx through NSCC-1 and NSCC-2 has an important role in the extracellular Ca2+ influx-dependent component of ERK1/2-dependent mitogenesis, (5) extracellular Ca2+ influx through NSCC-2 has an important role in ERK1/2-independent mitogenesis, and (6) Ca2+ influx through each Ca2+ channel may play a distinct role in intracellular mitogenic cascades.

Acetamides↗
PubMed2002

Nausea as a complication of low-frequency repetitive transcranial magnetic stimulation of the posterior fossa.

BACKGROUND: Transcranial magnetic stimulation (TMS) can non-invasively investigate the function of human brain. However, it can induce a focal pain at the stimulated site on the scalp or seizures when applied with high frequency (>1 Hz). Here we report an induction of nausea as a complication of low-frequency repetitive TMS (rTMS) of the cerebellum. SUBJECTS AND METHODS: Eight right-handed normal volunteers underwent low-frequency (0.9 Hz) rTMS of the right cerebellum. The stimulus intensity was set at 90% of the resting motor threshold determined by TMS to motor cortex. RESULTS: Nausea lasted as long as 10 min after the end of rTMS without apparent neurological deficit in two subjects. This symptom was replicated when the same protocol was applied on a different day in the same subjects. CONCLUSIONS: Low-frequency rTMS of cerebellum is still a safe procedure, but the experimenters should keep in mind the possibility of inducing nausea.

Adult↗
PubMed2002

Effects of combination chemotherapy with biscoclaurine-derived alkaloid (Cepharanthine) and nimustine hydrochloride on malignant glioma cell lines.

In the treatment of malignant glioma, chemotherapy plays a critical role as do surgical resection and irradiation. Cepharanthine (CEP), a biscoclaurine-derived alkaloid, reportedly potentiates the effects of antitumor agents and induces apoptosis in some cancer cells. Here, we examined the effects of CEP, alone and in combination with nimustine hydrochloride (ACNU), on the in vitro proliferation of malignant glioma cells. The cell lines used were U87MG, U251MG, and T98G. At concentrations from 1 to 10 microg/ml, CEP-promoted cell proliferation somewhat; growth inhibition was noted at concentrations of 15 microg/ml and higher. Phase-contrast microscopy showed that cells tended to detach from the culture dishes and that cell density became sparse at the higher concentrations. DAPI fluorescence nuclear staining revealed condensation and fragmentation of nuclei, indicating the induction of apoptosis. To examine the cascade of apoptosis, the caspase inhibitors YVAD and DEVD were added. They inhibited CEP-induced apoptosis in U251MG cells (a p53-mutant cell line), but not in U87MG cells (a p53 wild-type cell line), suggesting that in CEP-induced apoptosis two possible cascades are in play. In combination with ACNU, the effects of the higher concentrations of CEP were enhanced.

Alkaloids↗
PubMed2002

Characterization of G proteins involved in activation of nonselective cation channels by endothelin(B) receptor.

1: We recently demonstrated that endothelin-1 (ET-1) activates two types of Ca(2+)-permeable nonselective cation channels (NSCC-1 and NSCC-2) in Chinese hamster ovary cells expressing endothelin(B) receptors (CHO-ET(B)R) that couple with G(q) and G(i). The purpose of the present study was to identify the G proteins involved in the activation of these Ca(2+) channels by ET-1. For this purpose, we constructed CHO cells expressing an unpalmitoylated (Cys(402)Cys(403) Cys(405)-->Ser(402)Ser(403)Ser(405)) ET(B)R (CHO-SerET(B)R) and ET(B)R truncated at the cytoplasmic tail downstream of Cys(403) (CHO-ET(B)RDelta403). 2: Based on the data obtained from actin stress fibre formation, CHO-ET(B)R couple with G(13). Therefore, CHO-ET(B)R couple with G(q), G(i) and G(13). CHO-SerET(B)R and CHO-ET(B)RDelta403 couple with G(13) and G(q), respectively. 3: ET-1 activated NSCC-1 in CHO-ET(B)R preincubated with phospholipase C (PLC) inhibitor, U73122, and in CHO-SerET(B)R. On the other hand, ET-1 failed to activate Ca(2+) channels in CHO-ET(B)RDelta403. Microinjection of dominant negative mutants of G(13) (G(13)G225A) abolished activation of NSCC-1 and NSCC-2 in CHO-ET(B)R and that of NSCC-1 in CHO-SerET(B)R. 4: Y-27632, a specific Rho-associated kinase (ROCK) inhibitor, did not affect the ET-1-induced transient and sustained increase in [Ca(2+)](i) in CHO-ET(B)R. 5: These results indicate that (1) the cytoplasmic tail downstream of the palmitoylation sites of ET(B)R, but not the palmitoylation site itself, is essential for coupling with G(13), (2) the activation mechanism of each Ca(2+) channel by ET-1 is different in CHO-ET(B)R. NSCC-1 activation depends on G(13)-dependent cascade, and NSCC-2 activation depends on both G(q)/PLC- and G(13)-dependent cascades. Moreover, ROCK-dependent cascade is not involved in the activation of these channels.

Actins↗
PubMed2002

Low-frequency electric cortical stimulation has an inhibitory effect on epileptic focus in mesial temporal lobe epilepsy.

PURPOSE: This study was conducted to investigate the effect of low-frequency electric cortical stimulation on epileptic focus in humans. METHODS: We stimulated the epileptic focus in a patient with medically intractable mesial temporal lobe epilepsy (MTLE) by means of subdural electrodes and evaluated the change in the number of interictal epileptiform discharges. We used biphasic electric current of 0.3-ms duration presented at 0.9-Hz frequency for 250 s, comparing stimulus intensity of 7.5, 2, and 0.5 mA. RESULTS: Interictal epileptiform discharges at the ictal focus occurred less frequently after the stimulation with the intensity of 0.5 mA. With the intensity of 7.5 mA and 2.0 mA, however, habitual auras were elicited by the stimulation, and afterdischarges were seen on the cortical EEG. CONCLUSIONS: Low-frequency, low-intensity electric cortical stimulation could produce inhibitory effects on epileptic activity. At the same time, however, a caution for possible induction of EEG seizures is needed, even when applying low-frequency electric stimulation.

Adolescent↗
PubMed2002

Partial epilepsy manifesting atonic seizure: report of two cases.

PURPOSE: Atonic seizures are commonly seen in patients with generalized epilepsy but only infrequently in patients with partial epilepsy. Clinically generalized atonic seizures as a partial epilepsy have not been studied in detail with video/EEG monitoring. Here we describe the clinical and physiologic characteristics of atonic seizures due to partial epilepsy and discuss the underlying mechanism. METHODS: Two patients with partial epilepsy manifesting atonic seizures, one with frontal lobe epilepsy (FLE) and the other with parietal lobe epilepsy (PLE), were reported. The long-term video/EEG monitoring, magnetic resonance imaging (MRI), and interictal fluorodeoxyglucose-positron emission tomography (FDG-PET) were investigated in each patient. RESULTS: Paroxysmal diminution of muscle tone mainly involved the axial muscles in both patients. In contrast with the abrupt falls seen in patients with Lennox-Gastaut syndrome, the falls in these patients were slow, taking 2-5 s to fall down. Ictal EEG records showed low-voltage fast activity in the frontocentral area followed by repetitive spikes at the midline frontocentral area in the patient with FLE, and rhythmic spikes in the left central area in the patient with PLE. Interictal FDG-PET disclosed hypometabolic regions consistent with the clinical and EEG findings. CONCLUSIONS: Slow falls might be a feature of atonic seizures in partial epilepsy. Long-lasting atonia in partial epilepsy could be due to either one of the following two possible mechanisms: (a) epileptic activities arising from the negative motor area, of which 50-Hz electric stimulation causes motor inhibition, or (b) sustained atonia with successive electromyogram (EMG) silent periods caused by epileptic discharges arising from the inhibitory area of the primary sensorimotor area.

Adult↗
PubMed2002

Extracellular Ca2+ influx and endothelin-1-induced intracellular mitogenic cascades in rabbit internal carotid artery vascular smooth muscle cells.

Endothelin-1 (ET-1) has been proven to activate two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC) in rabbit internal carotid artery vascular smooth muscle cells (ICA VSMCs). Ca2+ influx through these channels plays an essential role for ET-1-induced mitogenesis in ICA VSMCs. The purpose of the current study was to investigate the effects of Ca2+ influx on intracellular pathways of ET-1-induced mitogenesis in ICA VSMCs using receptor-operated Ca2+ channel blockers, SK&F 96365 and LOE 908. We focused on extracellular-signal regulated kinase 1 and 2 (ERK1/2) in this context. PD 98059, an inhibitor of mitogen-activated protein kinase kinase, abolished the ET-1-induced increase in ERK1/2 activity, but only partially suppressed the mitogenesis. ERK1/2 activation by ET-1 was partially suppressed in the absence of extracellular Ca2+. Moreover, based on the sensitivity to SK&F 96365 and LOE 908, Ca2+ influx through NSCC-1, NSCC-2 and SOCC plays essential roles in the extracellular Ca2+-dependent component of ERK1/2 activity. In addition, Ca2+ influx through these channels was also involved in the PD 98059-resistant component of ET-1-induced mitogenesis. These results indicate that (1) the ET-1-induced mitogenesis involves both ERK1/2-dependent and -independent mechanisms in ICA VSMCs (2), ERK1/2 activation by ET-1 involves a Ca2+ influx-dependent cascade as well as a Ca2+ influx-independent cascade (3), Ca2+ influx through NSCC-1, NSCC-2 and SOCC has important roles in the Ca2+ influx-dependent component of ERK1/2-dependent mitogenesis, and (4) Ca2+ influx through these channels also plays important roles in mitogenic pathways downstream of ERK1/2.

Acetamides↗
PubMed2002

Characterization of Ca2+ channels involved in endothelin-1-induced contraction of rabbit basilar artery.

This study attempted to characterize Ca2+ channels involved in endothelin-1-induced contraction of rabbit basilar artery using whole-cell patch-clamp and measurement of intracellular free Ca2+ concentration. Endothelin-1 activates two types of Ca2+-permeable nonselective cation channels (NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC) in addition to the voltage-operated Ca2+ channel (VOCC). These channels can be discriminated using Ca2+ channel blockers, SK&F 96365 and LOE 908. Tension study was conducted to clarify the Ca2+ channels involved in endothelin-1-induced contraction of basilar artery. Endothelin-1-induced basilar artery contraction is fully dependent on extracellular Ca2+ influx. Based on sensitivity to nifedipine, an L-type VOCC blocker, VOCCs have a minor role in endothelin-1-induced contraction. Both LOE 908 and SK&F 96365 inhibit endothelin-1-induced contraction in a concentration-dependent manner, and their combination abolished it. The median inhibitory concentrations of these blockers for endothelin-1-induced contraction correlated well with those of the endothelin-1-induced [Ca2+]i responses. Thus, the inhibitory action of these blockers on endothelin-1-induced contraction may be mediated by blockade of NSCC-1, NSCC-2, and the SOCC. Extracellular Ca2+ influx through NSCC-1, NSCC-2, and SOCC may be essential for endothelin-1-induced basilar artery contraction.

Animals↗
PubMed2002

Overexpression of basic fibroblast growth factor and Bcl-xL with adenoviral vectors protects primarily cultured neurons against glutamate insult.

OBJECTIVE: Excitatory amino acid (EAA) toxicity seems to be an important mechanism of neuronal cell death after cerebral infarction. We examined the inhibitory effects of neuronal cell death caused by EAA in vitro by means of adenoviral gene transfer of neurotrophic basic fibroblast growth factor (bFGF) and antiapoptotic Bcl-xL. METHODS: Recombinant adenoviral vectors expressing human bFGF gene with secretory signals of interleukin-2 and human Bcl-xL gene were constructed. Primarily cultured rat neuronal cells were treated with glutamate to cause EAA, and the neuroprotective effects of gene transfer by these adenoviral vectors were investigated at several time points of infection. RESULTS: Each adenoviral infection to primarily cultured neuronal cells exhibited neuroprotective effects against EAA caused by glutamate. Both gene transfer of bFGF with secretory signal and Bcl-xL transfer to neuronal cells exhibited the synergistic neuroprotective effects against EAA. These effects were most prominent with gene transfer 4 hours before glutamate insult; gene transfer performed simultaneously with and up to 4 hours after the insult exhibited definite neuroprotective effects. CONCLUSION: These experiments revealed marked neuroprotective effects of adenoviral gene transfer of bFGF and Bcl-xL into neuronal cells in vitro. The findings may lead to new approaches for treating occlusive cerebrovascular disease.

Adenoviridae↗
PubMed2002

The Kabuto, or the Japanese helmet: evolution from war implement to status symbol.

WARRIORS THROUGHOUT THE AGES have considered the unprotected head to be particularly vulnerable. The traditional Japanese helmet, the Kabuto, was the part of a protective suit of armor that reflected the wearer's character and personality. Over time, it changed from a primarily protective device to a vehicle for the expression of a distinctly Japanese sense of magnificent artistry. Each Kabuto was custom-made, and these helmets remain without peer in the world. They were designed and crafted to answer the demands of their era, and thus they provide historical evidence not only of the state of Japanese warfare, but also of social organization, metallurgical knowledge, artisanship, and aesthetic sensibility. Even now, during the national Golden Week Festival in early May, Kabuto are displayed in the alcoves of Japanese homes as a petition that the boys in the house be granted courage and good health. Thus, even in modern Japan, the Kabuto represents a talisman. We present an overview of the evolution of the Kabuto, with special reference to the Japanese sword and the warrior tradition.

Head Protective Devices↗
PubMed2002

Increased expression of phosphorylated c-Jun amino-terminal kinase and phosphorylated c-Jun in human cerebral aneurysms: role of the c-Jun amino-terminal kinase/c-Jun pathway in apoptosis of vascular walls.

OBJECTIVE: Vascular remodeling via apoptotic mechanisms is an important factor in vascular diseases. c-Jun amino-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and initiates apoptosis mainly via phosphorylation of the c-Jun transcription factor. We performed this study to clarify the roles of the JNK/c-Jun pathway and apoptosis in the pathogenesis of cerebral aneurysms. METHODS: Cerebral aneurysms from 12 patients and control vessels from 5 patients were studied. We analyzed the expression of phosphorylated JNK and phosphorylated c-Jun in cerebral aneurysms by using immunohistochemical methods. RESULTS: Immunoreactivity for phosphorylated JNK and phosphorylated c-Jun was increased in the vascular walls of the cerebral aneurysms studied. Immunoreactivity for single-stranded deoxyribonucleic acid (a marker of deoxyribonucleic acid damage) was also increased in aneurysmal tissue, compared with control vessels, and was colocalized with that for phosphorylated JNK and phosphorylated c-Jun in smooth muscle cells. CONCLUSION: These observations may lead to better understanding of the role of the JNK/c-Jun pathway in the development of cerebral aneurysms and to new strategies for treatment.

Adult↗