1.HIPPO-integrin Linked Kinase Crosstalk Controls Self-sustaining Proliferation and Survival in Pulmonary Hypertension.
Kudryashova TV1, Goncharov DA2, Pena A3, Kelly N4, Vanderpool R5, Baust J6, Kobir A7, Shufesky W8, Mora AL9, Morelli AE10, Zhao J11, Ihida-Stansbury K12, Chang B13, DeLisser H14, Tuder RM15, Kawut SM16, Silljé HH17, Shapiro S18, Zhao Y19, Goncharova EA20. Am J Respir Crit Care Med. 2016 Apr 27. [Epub ahead of print]
RATIONALE: Enhanced proliferation and impaired apoptosis of pulmonary arterial vascular smooth muscle cells (PAVSMC) are key pathophysiological components of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH).
2.Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis.
Tudor JC1, Davis EJ1, Peixoto L1, Wimmer ME1, van Tilborg E1, Park AJ1, Poplawski SG1, Chung CW1, Havekes R1, Huang J2, Gatti E3, Pierre P3, Abel T4. Sci Signal. 2016 Apr 26;9(425):ra41. doi: 10.1126/scisignal.aad4949.
Sleep deprivation is a public health epidemic that causes wide-ranging deleterious consequences, including impaired memory and cognition. Protein synthesis in hippocampal neurons promotes memory and cognition. The kinase complex mammalian target of rapamycin complex 1 (mTORC1) stimulates protein synthesis by phosphorylating and inhibiting the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2). We investigated the involvement of the mTORC1-4EBP2 axis in the molecular mechanisms mediating the cognitive deficits caused by sleep deprivation in mice. Using an in vivo protein translation assay, we found that loss of sleep impaired protein synthesis in the hippocampus. Five hours of sleep loss attenuated both mTORC1-mediated phosphorylation of 4EBP2 and the interaction between eukaryotic initiation factor 4E (eIF4E) and eIF4G in the hippocampi of sleep-deprived mice. Increasing the abundance of 4EBP2 in hippocampal excitatory neurons before sleep deprivation increased the abundance of phosphorylated 4EBP2, restored the amount of eIF4E-eIF4G interaction and hippocampal protein synthesis to that seen in mice that were not sleep-deprived, and prevented the hippocampus-dependent memory deficits associated with sleep loss.
3.Suppression of REDD1 in osteoarthritis cartilage, a novel mechanism for dysregulated mTOR signaling and defective autophagy.
Alvarez-Garcia O1, Olmer M1, Akagi R2, Akasaki Y1, Fisch KM1, Shen T1, Su AI1, Lotz MK3. Osteoarthritis Cartilage. 2016 Apr 23. pii: S1063-4584(16)30050-4. doi: 10.1016/j.joca.2016.04.015. [Epub ahead of print]
OBJECTIVE: Aging is a main risk factor for the development of osteoarthritis (OA) and the molecular mechanisms underlying the aging-related changes in articular cartilage include increased mammalian target of rapamycin (mTOR) signaling and defective autophagy. REDD1 is an endogenous inhibitor of mTOR that regulates cellular stress responses. In this study we measured REDD1 expression in normal, aged and OA cartilage and assessed REDD1 function in human and mouse articular chondrocytes.
