BACKGROUNDHuman piebaldism is a rare autosomal dominant condition characterized by congenital white forelock and depigmented patches of skin, typically on the forehead, anterior trunk and extremities. Mutations in the KIT gene have been proposed to be responsible for the underlying changes in this disorder. The aim of this study was to identify gene mutation in a Chinese family with piebaldism.

METHODSA Chinese family with piebaldism presenting with white forelock and large depigmented skin macules on the abdomen, arms and legs was collected. DNA was isolated from peripheral blood of the family members. The encoding exons with flanking intron regions of the KIT gene were analyzed by polymerase chain reactions (PCR) and direct DNA sequencing. Besides, DNA extracted from 100 ethnically matched population individuals was as controls.

RESULTSA heterozygous missense mutation c.2590T > C was identified in the patients of the family. This mutation converted a serine residue to proline (p.Ser864Pro). The mutation was not found in their unaffected family members or normal controls.

CONCLUSIONA novel missense mutation c.2590 T > C was found and it might play a significant role in the piebaldism phenotype in the family.

Child ; Humans ; Male ; Mutation, Missense ; Piebaldism ; genetics ; Proto-Oncogene Proteins c-kit ; genetics ; physiology

Pim-1 belongs to a family of serine/threonine protein kinases that are highly conserved through evolution in multicellular organisms. Originally identified from moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice, Pim-1 kinase is involved in the control of cell growth, differentiation and apoptosis. Expression of Pim-1 kinase can be stimulated by a variety of growth factors and regulated at four different levels: transcriptional, post-transcriptional, translational and post-translational. Several signal transduction pathways may be associated with the regulation of Pim-1's expression; accumulating data support that the expression of Pim-1 protein is mediated through activation of JAK/STATs. Recent studies of Pim family kinases indicate that Pim-1 kinase plays important roles outside of the hematopoietic system as well.
Animals ; Apoptosis/*physiology ; Cell Differentiation/physiology ; Cell Division/*physiology ; *Cell Transformation, Neoplastic ; Gene Expression Regulation, Enzymologic ; Humans ; Lymphoma/etiology ; Mice ; Protein-Serine-Threonine Kinases/genetics/*physiology ; Proto-Oncogene Proteins/genetics/*physiology ; Proto-Oncogene Proteins c-pim-1 ; Signal Transduction

BACKGROUNDTransient sublethal ischemia is known as ischemic preconditioning, which enables cells and tissues to survive subsequent prolonged lethal ischemic injury. Ischemic preconditioning exerts neuroprotection through phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Cbl-b belongs to the Casitas B-lineage lymphoma (Cbl) family, and it can regulate the cell signal transduction.The roles of ubiquitin ligase Cbl-b and PI3K/Akt pathway and the relationship between them in oxygen-glucose deprivation preconditioning (OGDPC) in PC12 cells were investigated in the present study.

METHODSOxygen and glucose deprivation (OGD) model in PC12 cells was used in the present study. The 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, nuclear staining with Hoechst 33258, and Western blotting were applied to explore the roles of Cbl-b and PI3K/Akt pathway and the relationship between them in OGDPC in PC12 cells.

RESULTSCell viability was significantly changed by OGD and OGDPC. OGD significantly decreased cell viability compared with the control group (P < 0.05), and preconditioning could rescue this damage was demonstrated by the increase of cell viability (P < 0.05). The expression of Cbl-b was significantly increased after OGD treatment. However, the activation of Akt and GSK3β was greatly inhibited. Preconditioning could inhibit the increase of Cbl-b caused by OGD and increase the activation of Akt and GSK3β. LY294002, a specific inhibitor of PI3K, could effectively inhibit the increase of Akt and GSK3β after preconditioning treatment. It partly inhibited the decrease of Cbl-b expression after preconditioning treatment.

CONCLUSIONUbiquitin ligase Cbl-b and PI3K/Akt pathway are differently involved in OGDPC in PC12 cells.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Animals ; Cell Survival ; Glucose ; deficiency ; Ischemic Preconditioning ; Oxygen ; metabolism ; PC12 Cells ; Phosphatidylinositol 3-Kinase ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Proto-Oncogene Proteins c-cbl ; genetics ; metabolism ; Rats ; Signal Transduction ; physiology

Autophagy is fundamental to maintain cellular homeostasis. As one kind of the most well-studied selective autophagy, autophagy of mitochondria (mitophagy)is crucial for the clearance of damaged mitochondria. Mitophagy dysfunction has been proved to be closely associated with many human diseases. Nix is a key protein for mitophagy during the maturation of reticulocytes. However, the detailed molecular mechanisms underlying Nix-mediated mitophagy are not fully understood. This article summarizes three possible working models of Nix in mitophagy induction. Firstly, Nix can interplay with Parkin, another important protein for mitophagy, to initiate mitophagy. Secondly, Nix can serve as a receptor for autophagy machinery by interacting with Atg8 family through its LIR motif. Finally, as a BH3-only protein, Nix can compete with Beclin-1 to bind other members of Bcl-2 family resulting in increased free Beclin-1 in cytosol, which further promotes autophagy flux.
Autophagy ; genetics ; physiology ; Autophagy-Related Protein 8 Family ; physiology ; Beclin-1 ; physiology ; Membrane Proteins ; physiology ; Mitochondria ; genetics ; physiology ; Mitochondrial Degradation ; genetics ; physiology ; Protein Interaction Domains and Motifs ; Proto-Oncogene Proteins ; physiology ; Proto-Oncogene Proteins c-bcl-2 ; antagonists & inhibitors ; Tumor Suppressor Proteins ; physiology ; Ubiquitin-Protein Ligases ; physiology

Self-renewal of hematopoietic stem cells is vital for the sustained daily production of blood cells. The Bmi-1 gene is a putative oncogene belonging to the Polycomb group family. Recent studies have shown that the Polycomb-group gene Bmi-1 is indispensable for regulation of self-renewal of normal and leukemic stem cells. The research progress on structure and function of Bmi-1 gene, and its role in self-renewal of hematopoietic stem cells was reviewed.
Cell Differentiation ; physiology ; Cell Division ; physiology ; Hematopoietic Stem Cells ; cytology ; physiology ; Humans ; Nuclear Proteins ; genetics ; physiology ; Polycomb Repressive Complex 1 ; Proto-Oncogene Proteins ; genetics ; physiology ; Repressor Proteins ; genetics ; physiology

The stress environment regulates the factors of growth, resorption and remolding in bone tissue. Mechanical stimulation at cell physical level affects the physiological activity of osteoblasts, including proliferation, ALP activity and osteocalcin production. Mechanotransduction is a procedure which transduces the biophysical force into biochemical responses. It is also the basis of many physiological functions. The early response genes (c-fos, c-jun), the second message systems (Ca2+, NO, cAMP) and the mechano-sensitive cation channel are involved in the mechanotransduction course when osteoblasts respond to the mechanical stimulation.
Biomechanical Phenomena ; Calcium ; physiology ; Humans ; Mechanotransduction, Cellular ; Osteoblasts ; physiology ; Osteocalcin ; biosynthesis ; Proto-Oncogene Proteins c-fos ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-jun ; biosynthesis ; genetics ; Signal Transduction ; Stress, Mechanical

Apoptosis ; Cell Cycle ; Cell Differentiation ; Cell Proliferation ; Humans ; Neoplastic Processes ; Proto-Oncogene Proteins c-jun ; genetics ; metabolism ; physiology

OBJECTIVETo study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats.

METHODSAqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method.

RESULTSPeripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05).

CONCLUSIONH. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Agaricales ; chemistry ; Animals ; Axons ; pathology ; Female ; Ganglia, Spinal ; metabolism ; Glucans ; analysis ; MAP Kinase Signaling System ; Nerve Crush ; Nerve Regeneration ; physiology ; Peripheral Nerves ; enzymology ; physiology ; Peroneal Nerve ; physiology ; Protein Biosynthesis ; Proto-Oncogene Proteins c-akt ; metabolism ; Proto-Oncogene Proteins c-fos ; genetics ; metabolism ; Proto-Oncogene Proteins c-jun ; genetics ; metabolism ; Rats, Sprague-Dawley

Cell Movement ; genetics ; physiology ; Humans ; Microfilament Proteins ; genetics ; metabolism ; Models, Biological ; Neoplasm Metastasis ; genetics ; physiopathology ; Protein Binding ; genetics ; physiology ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Vesicular Transport Proteins ; genetics ; metabolism

In order to study the potential effects of exogenous WT1 gene isoform on apoptosis in leukemia cell line NB4 and its possible molecular mechanisms, the eukaryotic expression recombinant vector (pCB6(+)/WTA) containing full-length human WT1 isoform (WTA: -17aa/-KTS) cDNA and the vacant vector-alone were introduced into the leukemia cell line NB4 respectively by electroporation. The WTA mRNA and protein in cells were detected by RT-PCR and Western blot. Binding of Annexin V were tested by flow cytometry and agarose gel electrophoresis to verify whether exogenous WTA could induce apoptosis of NB4 cells. Expressions of p21, p53, bcl-2, bcl-XL and c-myc genes were determined by semi-quantitative RT-PCR after introducing recombinant vectors into the NB4 cells. The results showed that in exposure to As(2)O(3) at 0.8 micromol/L for 48 hours, the NB4/WTA cells exhibited the morphological hallmarks of apoptosis, the marked DNA ladder shown by gel electrophoresis, and the enhanced apoptosis rate marked by Annexin V. RT-PCR showed an increase in p21 and c-myc genes expression, a decrease in bcl-2 and a relative constant expression of p53, bcl-XL in NB4/WTA cells. It is concluded that the introduction and expression of exogenous WTA gene can lead to apoptosis of NB4/WTA cells by down-regulating the Bcl-2 gene expression and up-regulating the p21 and c-myc genes expression.
Apoptosis ; genetics ; physiology ; Blotting, Western ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Proto-Oncogene Proteins c-myc ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Tumor Suppressor Protein p53 ; genetics ; WT1 Proteins ; genetics ; metabolism ; physiology ; bcl-X Protein ; genetics