Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells

Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells.     

Failure properties of vena cava tissue due to deep penetration during filter insertion

In this work, we use an in-vitro mechanical test to explore the resistance of biaxially stretched vena cava tissue against deep perforation and a methodology which integrates experimental and numerical modeling to identify constitutive fracture properties of the vena cava. Six sheep vena cava were harvested just after killing, and cyclic uniaxial tension tests in longitudinal and circumferential directions and biaxial deep penetration tests were performed. After that, we use a nonlinear finite element model to simulate in vitro penetration of the cava tissue in order to fit the fracture properties under penetration of the vena cava by defining a cohesive fracture zone. An iterative process was developed in order to fit the fracture properties of the vena cava using the previously obtained experimental results. The proposed solutions were obtained with fracture energy of 0.22 or 0.33 N/mm. In comparison with the experimental data, the simulation using \(\delta _{0}=0.01\,\hbox {mm}\), \(\delta _{r}=0.35\,\hbox {mm}\), and \(K=220\, \hbox {N}/\hbox {mm}^{3}\) parameters (\(F_{\hbox {max}}=0.92\)) is in good agreement with results from penetration experiments of cava tissue. It is noticeable that the parameter estimation process of the fracture behavior is more accurate than the estimation process of the elastic behavior for the toe region of the curve.     

GADD45B mediates podocyte injury in zebrafish by activating the ROS-GADD45B-p38 pathway

GADD45 gene has been implicated in cell cycle arrest, cell survival or apoptosis in a cell type specific and context-dependent manner. Members of GADD45 gene family have been found differentially expressed in several podocyte injury models, but their roles in podocytes are unclear. Using an in vivo zebrafish model of inducible podocyte injury that we have previously established, we found that zebrafish orthologs of gadd45b were induced upon the induction of podocyte injury. Podocyte-specific overexpression of zebrafish gadd45b exacerbated edema, proteinuria and foot-process effacement, whereas knockdown of gadd45b by morpholino-oligos in zebrafish larvae ameliorated podocyte injury. We then explored the role of GADD45B induction in podocyte injury using in vitro podocyte culture. We confirmed that GADD45B was significantly upregulated during the early phase of podocyte injury in cultured human podocytes and that podocyte apoptosis induced by TGF-β and puromycin aminonucleoside (PAN) was aggravated by GADD45B overexpression but ameliorated by shRNA-mediated GADD45B knockdown. We also showed that ROS inhibitor NAC suppressed PAN-induced GADD45B expression and subsequent activation of p38 MAPK pathway in podocytes and that inhibition of GADD45B diminished PAN-induced p38 MAPK activation. Taken together, our findings demonstrated that GADD45B has an important role in podocyte injury and may be a therapeutic target for the management of podocyte injury in glomerular diseases.Podocyte dysfunction, injury or loss is a common and decisive cause of various glomerular diseases and understanding the molecular mechanism underlying podocyte response to stress will be very helpful to undermine the pathogenesis of podocyte injury and the targeted therapy for glomerular diseases.The members of Gadd45 gene family, Gadd45a, Gadd45b and Gadd45r have been commonly implicated in stress signaling in response to physiological or environmental stressors, resulting in cell cycle arrest, DNA damage repair, cell survival, senescence and apoptosis.¹ Recently, this gene family has been found differentially expressed in several podocyte injury models. Zhang et al.² observed an induction of GADD45β mRNA expression by lipopolysaccharide in the lung, kidney and spleen, which had the highest GADD45β mRNA expression among all of the tissues examined. Jeffrey W Pippin reported that protein expression of GADD45 was increased in glomeruli from passive Heymann nephritis rats and cultured podocytes exposed in vitro to C5b-9. ³ More recently, Shi et al.⁴ reported that Gadd45b was upregulated in glomeruli of mice with podocyte-specific deletion of Dicer, suggesting the involvement of Gadd45b in podocyte injury. However, no functional characterization of Gadd45 genes in podocytes has been conducted to date and the role of GADD45B in the context of podocyte injury remains unclear.Zebrafish has emerged as a new vertebrate model system for renal glomerular research. The podocytes and renal glomeruli in zebrafish kidney are structurally, molecularly and functionally conserved, rendering zebrafish a valuable and relevant model for podocyte studies. To characterize the role of GADD45b in podocyte injury, we therefore employed zebrafish as an in vivo model system and human podocytes as an in vitro model. We observed the upregulation of GADD45B on podocyte injury in zebrafish renal glomeruli as well as in cultured human podocytes treated with TGF-β and PAN. We further showed that podocyte-specific overexpression of zebrafish orthologs of gadd45b predisposed podocytes to injury, whereas inhibition of gadd45b expression in zebrafish larvae ameliorated podocyte injury and reduced proteinuria. Furthermore, we found that the ROS-GADD45B-p38 pathway was involved in the regulation of GADD45B expression and deleterious role in podocyte injury. Collectively, we have identified GADD45B as an important player in podocyte injury.     

Length–weight relationships of two fish species from the Yangtze River,China

Fish samples for the study were collected from the Yangtze River in China. Length–weight relationships were determined for two endemic fish species (Leiocassis longirostris Günther, 1864 and Schistura fasciolata Nichols & Pope, 1927) for the first time.     

Isolation a P450 gene in <Emphasis Type="Italic">Pinus armandi</Emphasis> and its expression after inoculation of <Emphasis Type="Italic">Leptographium qinlingensis</Emphasis> and treatment with methyl jasmonate

In conifers, the cytochrome P450 monooxygenase of the CYP720B family plays an important role in the synthesis of diterpene resin acids, which are specialised metabolites of the oleoresin defence. We isolated CYP720B19 from Pinus armandi and found that it belongs to the CYP720B family. The CYP720B19 open reading frame of 1467 bp encodes a protein of 488 amino acid residues with high similarity to abietadienol/abietadienal oxidase. Differential expression of the CYP720B19 gene significantly changed when plants were inoculated with the fungus Leptographium qinlingensis, mechanically wounded, or treated with methyl jasmonate (MeJa) and Tween at 4 days and 8 days. Increased expression of the CYP720B19 gene after these treatments suggested that the gene was involved in pine defence against inoculation by L. qinlingensis, MeJa treatment and mechanical injury.