Clusterin (CLU) is a multifunctional glycoprotein that has secretory and nuclear isoforms. The two isoforms are known to play opposite roles in cell survival/death. In this review, we summarize recent progress on the pro-apoptotic function of nuclear CLU in vitro and in vivo and discuss previous reports on the role of CLU in brain damage and neurodegeneration.
Apoptosis ; Brain ; Clusterin ; Glycoproteins ; Protein Isoforms

No abstract available.
Gingiva* ; Periodontitis ; Protein Isoforms* ; Superoxide Dismutase* ; Superoxides*

Acute promyelocytic leukemia (APL) is characterized by a specific t (15;17) translocation which produce a PML/RAR-alpha fusion messenger RNA and by effectiveness of all-trans retinoic acid (ATRA) differentiation therapy. Breakpoints within PML intron 3 (bcr 3) produce a short PML/RAR-alpha isoform (S-isoform), whereas breakpoints within PML intron 6 (bcr 1) result in a longer form (L-isoform). Additionally, breakpoints within PML exon 6 (bcr 2) make a variable length transcript (V-isoform) in a small number of patients. The influence of breakpoint site on patient outcome remains controversial. Previous reports showed that patients with S-isoform have an increased incidence of clinical relapse and shorter survival compared to those with L-isoform. Others reported no difference in DFS between these patients groups. In this issue, Lee et al. reported that there were 58 L-isoform (62.1%), 32 S-isoform (34.0%), 4 V-isoform (4.3%) and, no significant prognostic factor for EFS from induction therapy using anthracycline plus ATRA among 94 patients with APL. They concluded pretreatment clinical characteristics and treatment outcomes were not significantly different according to PML/RAR-alpha isoform types in this induction group. Recently, it was reported that FLT3/ITD mutation was frequently associated with S-isoform and with the M3v form of leukemia and CNS relapse in APL was mostly related to S-isoform. With previous studies including this article, outcomes of different types of PML/RAR-alpha isoforms are not conclusive. Future researches need to be focused not only on clinical outcomes of different types of PML/RAR-alpha isoforms, but also clinical relevance of PML/RARA-alpha mRNA isoforms with other prognostic factors and particular clinical characteristics.
Exons ; Humans ; Incidence ; Introns ; Leukemia ; Leukemia, Promyelocytic, Acute ; Protein Isoforms ; Recurrence ; RNA Isoforms ; RNA, Messenger ; Tretinoin

Ischemic preconditioning (IPC) is a phenomenon that a brief episode of ischemia to a tissue renders the tissue resistance from a subsequent prolonged ischemia. It is generally accepted that this protection is a receptor-mediated process, and is realized via signal transduction pathways. Protein kinase C (PKC), known to play key regulatory roles in cellular processes, has been proposed as a primary cellular mediator of preconditioning. However, the role of PKC in eliciting cardioprotection remains controversial. The evidences for the 'PKC hypothesis' of preconditioning in various tissue and organs are summarized. Especially in intestine, a brief ischemia induced a reversible epithelial injury to the jejunum that is associated with activation of several PKC isoforms. Injury induced by an additional period of ischemia is reduced by the prior IPC, and this effect is abolished by non-selective PKC inhibition but not by a selective inhibitor of cPKC/or PKCdelta. This result suggest that activation of nPKC isoform (especially PKCepsilon) during and following ischemic insults may play an important role in protection against I/R injury in the intestine, and this mechanism is identical with previous study in heart tissue.
Heart ; Intestines ; Ischemia ; Ischemic Preconditioning* ; Jejunum ; Protein Isoforms ; Protein Kinase C* ; Protein Kinases* ; Signal Transduction

Activation of c-Jun N-terminal kinase (JNK) is associated with a wide range of disparate cellular responses to extracellular stimuli. In mammals, three JNK isoforms are known, and their differential regulation occurs in a stimulus- or a cell type-dependent manner. However, the underlying mechanism of this differential regulation has not been clearly elucidated. Here we demonstrated that JNK1 and JNK3 were activated in SH-SY5Y cells after treatment with H2O2 or UV. In SH-SY5Y cells overexpressing mJIP1, a splicing variant of a JNK scaffold protein JIP1, the H2O2-induced activities of both JNK1 and JNK3 were significantly suppressed. In the same cell line, however, UV-induced JNK1 activity was significantly suppressed, but JNK3 activity was not. During the RA-induced differentiation of SH-SY5Y cells, JNK1 was activated, whereas JNK3 was not, and this JNK1 activation was completely abolished in the cells overexpressing mJIP1. These results suggest that JIP1 plays a role in the regulation of the isoform-specific activation of JNKs in stimulus-dependent manner.
Cell Line ; Humans* ; JNK Mitogen-Activated Protein Kinases ; Mammals ; Neuroblastoma* ; Protein Isoforms

Alternative Splicing ; Fibronectins/genetics* ; Forensic Medicine ; Humans ; Protein Conformation ; Protein Isoforms/genetics* ; Wound Healing/physiology*

Wnt5a is a secreted Wnt ligand that plays a critical role in cellular pathways and inflammatory diseases. The WNT5A gene encodes two protein isoforms, Wnt5a-long and Wnt5a-short, which differ based on different promoter methylation and have distinct functions. However, the mechanisms of the promoter methylation are unclear. Depending on the extent of promoter methylation, Wnt5a exerts both anti-inflammatory and pro-inflammatory effects in inflammatory diseases, which may be involved in different Wnt5a isoforms. Therefore, the Wnt5a isoforms may be potential diagnostic markers for inflammatory diseases and the mechanisms of the WNT5A gene promoter methylation need to be further investigated.
DNA Methylation ; Wnt-5a Protein ; Promoter Regions, Genetic ; Protein Isoforms/genetics*

BACKGROUND AND OBJECTIVES: Protein kinase C (PKC) is known to be related with development of various cells. In the heart, each isoform reacts differentially against agonists and the reaction changes during development. In this study, the roles of PKC isoforms (alpha, beta, gamma, delta, epsilon, zeta) were investigated through the localization of mRNA expression in the developing rat heart with in situ hybridization histochemistry. MATERIALS AND METHOD: The mRNA expression pattern of PKC isoforms (alpha, beta, gamma, delta, epsilon, zeta) was investigated with in situ hybridization histochemistry in developing and adult rat hearts. Whole body parasagittal sections were used for embryonal day 14 (E14), E16, E18 and heart sections were used for just born (P0), postnatal day 7 (P7), P14, P21 and adult rat. RESULTS: The expression of PKC alpha was found from E14, peaked at P7, and gradually decreased to adult level. The expression of PKC beta was observed from P14, peaked at P21, and decreased to adult level. The expression of PKC delta in the heart was observed from E14, peaked at P0, and abruptly disappeared at P14. The expression of PKC epsilon was observed from E14, peaked at P0, after that gradually decreased and disappeared at adult rat heart. The expression of PKC gamma and zeta was not found from any stage of developing rat heart. CONCLUSION: From these results, it is suspected that each PKC isoform may be differentially related with development of heart. The strong expression of PKC alpha, delta, epsilon around perinatal period, rapidly developing stage, suggests that PKC alpha, delta, epsilon may be related with rapid development of rat heart. And the late postnatal expression of PKC beta suggests that PKC beta may be related with maturation of rat heart.
Adult ; Animals ; Heart* ; Humans ; In Situ Hybridization ; Protein Isoforms ; Protein Kinase C* ; Protein Kinase C-epsilon ; Protein Kinases* ; Rats* ; RNA, Messenger*

BACKGROUND: It is well established that vascular contraction is caused by not only an increase in cytosolic Ca2+ level but also activations of Ca2+-sensitizing mechanisms including protein kinase C (PKC) and low molecular GTP binding protein. However, the roles of PKC and RhoA, a low molecular GTP-binding protein, on the receptor agonist-mediated contraction in swine pulmonary artery has not been clarified. In the present study, we examined the contribution of PKC isoform and RhoA to the arterial stimulants-induced contraction in swine pulmonary artery. METHOD: The large (> 5 mm), medium (1-3 mm) and small (< 1 mm in outer diameter) sized pulmonary arteries were excised and the contractions were recorded isometrically. The contents and subcellular distribution of PKC isoforms and RhoA were detected using immunoblotting. RESULTS: In medium pulmonary artery, norepinephrine (NE, 10 nM-30micrometer) led contraction in a dose-dependent manner. In large and small pulmonary arteries, however, NE failed to induce a contraction. Adding of 12-deoxyphorbol 13-isobutyrate (DPB, 1micrometer), a PKC activator, developed muscle force in 1 mM EGTA-contained Ca2+-free physiological salt solution. The expressions of PKC alpha, elsilon were significantly increased in medium pulmonary artery. NE (10micrometer) evoked the translocation of RhoA from cytosol to the membrane but not those of PKC isoforms. In Ca2+-free physiological salt solution, DPB (1micrometer) caused a translocation of PKC isoforms. CONCLUSIONS: These results support that NE induces contraction via RhoA pathway but not PKC pathway in swine pulmonary artery.
Cytosol ; GTP Phosphohydrolases* ; GTP-Binding Proteins ; Immunoblotting ; Membranes ; Norepinephrine ; Protein Isoforms ; Protein Kinase C* ; Protein Kinases* ; Pulmonary Artery* ; Swine*

PURPOSE: Extraocular muscle (EOM) consists of two layers, orbital and global layers which are readily distinguished by their histology. This study was conducted to investigate the changes of histology, myosin heavy chain (MHC), and MHC isoforms of the global and orbital layers of EOM after tenotomy. METHODS: Forty-two New Zealand white rabbits were used. The rectus muscles were harvested at day 3, week 1, week 2, week 4, and week 8 after EOM tenotomy. EOM mass change was measured. The EOM were serially sectioned in coronal plane and stained with Masson's trichrome. The diameters of muscle fibers and cross sectional areas of two layers were measured in the middle of the muscles. Changes of MHC isoforms were also measured using immunohistochemistry. RESULTS: The EOM mass was decreased at all periods of surgery especially at day 3 and week 1, increased maximally at week 8. The diameters of EOM fibers in global layer were decreased at day 3, week 1, and week 2 after EOM tenotomy and increased maximally at week 8. The immunohistochemical stains of fast and slow MHC were weakened in the global layer at week 1 after tenotomy. CONCLUSIONS: EOM changes due to atrophy appeared at day 3, week 1, and week 2 after EOM tenotomy while EOM atrophy was recovered at week 4 and week 8 after the surgery. These changes did not appear on the EOM orbital layer but was shown in EOM global layer. These results were due to the histological and functional differences between the EOM global and orbital layers.
Atrophy ; Coloring Agents ; Immunohistochemistry ; Muscles ; Myosin Heavy Chains ; Orbit ; Protein Isoforms ; Rabbits ; Tenotomy*