The anemia of inflammation, commonly observed in patients with chronic infections, malignancy, trauma, and inflammatory disorders, is a well-known clinical entity. Until recently, we understood little about its pathogenesis. It now appears that the inflammatory cytokine IL-6 induces production of hepcidin, an iron-regulatory hormone that may be responsible for most or all of the features of this disorder.
Nancy C. Andrews
Intrahepatic proteolysis is a major determinant of secretion of ApoB-containing lipoproteins into plasma. Stimulation of post-ER presecretory proteolysis (PERPP) of ApoB by n-3 polyunsaturated fatty acids has been found to result in reduced secretion of VLDL particles by hepatocytes. A new study has shown that this stimulation is promoted by pro-oxidant conditions that result in increased hepatic lipid hydroperoxide content. Conversely, PERPP is suppressed by antioxidants and by saturated fatty acids, which are not susceptible to lipid peroxidation. Hence reduction of oxidative stress may have the unexpected side effect of increasing plasma lipid levels.
Ronald M. Krauss
The gene encoding dysbindin-1 has recently been implicated in susceptibility to schizophrenia. In this issue of the JCI, Talbot et al. show that, contrary to expectations, dysbindin-1 is located presynaptically in glutamatergic neurons and is reduced at these locations in schizophrenia . Further studies of dysbindin-1 and the proteins with which it interacts can be expected to throw light on the pathogenesis of schizophrenia.
Michael J. Owen, Nigel M. Williams, Michael C. O’Donovan
Neurodegeneration occurs in the majority of the more than 40 known lysosomal storage diseases. Since the nervous system in these disorders can be globally affected, effective treatment would require persistent widespread correction. Biffi et al. show such correction is possible in a mouse model of metachromatic leukodystrophy by the transplantation of hematopoietic cells genetically modified to overexpress the missing lysosomal enzyme. The results reveal a nervous system damage-response pathway that can be harnessed to provide therapy to the nervous system in these serious disorders.
Richard L. Proia, Yun-Ping Wu
Numerous stimuli activate Big MAPK-1 (BMK1), an MAPK that activates the myocyte enhancer factor-2 (MEF2) transcription factor. Conditional gene deletion showed BMK1 to be required for survival of endothelial cells. An active form of MEF2C could partially bypass the requirement for BMK1 for endothelial cell survival in vitro. These findings reveal an essential role for BMK1-MEF2 signaling in an endothelial cell survival pathway and raise interesting questions about the molecular basis of this response.
Eric N. Olson
Lipogenesis is regulated by sterols and by insulin through the regulated expression and activation of the sterol regulatory element–binding proteins (SREBPs). A new study shows one way in which sterol and insulin regulation can be decoupled. In transgenic mice overexpressing a protein that regulates SREBP activation, lipogenesis is more sensitive to cholesterol and less sensitive to insulin.
Alan D. Attie
Understanding of autoimmune sensorineural hearing loss (ASNHL) has been hindered by the inaccessibility of the inner ear to biopsy and the lack of workable animal models. A report in this issue of the JCI describes a mouse model of CD4+ T cell–mediated ASNHL induced by immunization with peptides from the inner ear–specific proteins cochlin and β-tectorin.
Peter Billings
The factors that contribute to the development of B cell chronic lymphocytic leukemia (B-CLL) are unknown, and the groups of individuals at the greatest risk for developing this common leukemia are not well defined. Molecular features are important for classifying cases of B-CLL, and it is now apparent that similarities among Ig rearrangements between patients may give important clues to the origin of this disease.
Grant R. Kolar, J. Donald Capra
Previous animal studies have demonstrated that the loss of the β1 subunit of the large-conductance Ca2+-activated K+ (BK) channel leads to hypertension. A new study demonstrates that a gain in β1 subunit function is associated with protection against diastolic hypertension in humans, underscoring the importance of the β1 subunit and the BK channel in the regulation of vascular resistance.
Mark T. Nelson, Adrian D. Bonev
Failure in the peristaltic mechanism that conducts urine from the kidney to the bladder can lead to hydronephrosis, a common birth defect associated with obstructive nephropathy. New animal models reveal molecular pathways important for peristalsis and point to the central role of the renal pelvis in urine transport.
Cathy Mendelsohn
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