Rats, Transgenic

Publication Title: 
PloS One

BACKGROUND: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the lumbar spinal cord of SOD1(G93A) rats leads to a moderate therapeutical effect as evidenced by local ?-motoneuron sparing and extension of lifespan.

Author(s): 
Hefferan, Michael P.
Galik, Jan
Kakinohana, Osamu
Sekerkova, Gabriela
Santucci, Camila
Marsala, Silvia
Navarro, Roman
Hruska-Plochan, Marian
Johe, Karl
Feldman, Eva
Cleveland, Don W.
Marsala, Martin
Publication Title: 
Clinical journal of the American Society of Nephrology: CJASN

BACKGROUND: Because of the risk of performing renal biopsies in children with co-morbid conditions, we carried out this study to identify candidate protein biomarkers in the urine of HIV-infected children with renal disease. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Urine samples from HIV-infected children with biopsy proven HIV-nephropathy (HIVAN; n = 4), HIV-associated Hemolytic Uremic Syndrome (HIV-HUS; n = 2), or no renal disease (n = 3) were analyzed by two-dimensional electrophoresis (2-DE) and proteomic methods.

Author(s): 
Soler-García, Angel A.
Johnson, Douglas
Hathout, Yetrib
Ray, Patricio E.
Publication Title: 
Antioxidants & Redox Signaling

We studied the subcellular distribution of mitochondria and superoxide dismutase-1 (SOD1) in whole mounts of microdissected motor axons of rats expressing the ALS-linked SOD1-G93A mutation. The rationale was to determine whether physical interactions between the enzyme and mitochondria were linked to the axonopathy of motor fibers occurring in amyotrophic lateral sclerosis (ALS). Mitochondria and SOD1 displayed a homogeneous distribution along motor axons both in nontransgenic rats and in those overexpressing wild-type SOD1.

Author(s): 
Sotelo-Silveira, Jose R.
Lepanto, Paola
Elizondo, Victoria
Horjales, Sofia
Palacios, Florencia
Martínez-Palma, Laura
Marin, Monica
Beckman, Joseph S.
Barbeito, Luis
Publication Title: 
Neurobiology of Disease

Exposure to environmental lead (Pb) is a mild risk factor for amyotrophic lateral sclerosis (ALS), a paralytic disease characterized by progressive degeneration of motor neurons. However, recent evidence has paradoxically linked higher Pb levels in ALS patients with longer survival. We investigated the effects of low-level Pb exposure on survival of mice expressing the ALS-linked superoxide dismutase-1 G93A mutation (SOD1(G93A)). SOD1(G93A) mice exposed to Pb showed longer survival and increased expression of VEGF in the ventral horn associated with reduced astrocytosis.

Author(s): 
Barbeito, Ana G.
Martínez-Palma, Laura
Vargas, Marcelo R.
Pehar, Mariana
Mañay, Nelly
Beckman, Joseph S.
Barbeito, Luis
Cassina, Patricia
Publication Title: 
Analytical Biochemistry

Metals are key cofactors for many proteins, yet quantifying the metals bound to specific proteins is a persistent challenge in vivo. We have developed a rapid and sensitive method using electrospray ionization mass spectrometry to measure Cu,Zn superoxide dismutase (SOD1) directly from the spinal cord of SOD1-overexpressing transgenic rats. Metal dyshomeostasis has been implicated in motor neuron death in amyotrophic lateral sclerosis (ALS). Using the assay, SOD1 was directly measured from 100 μg of spinal cord, allowing for anatomical quantitation of apo, metal-deficient, and holo SOD1.

Author(s): 
Rhoads, Timothy W.
Lopez, Nathan I.
Zollinger, Daniel R.
Morré, Jeffrey T.
Arbogast, Brian L.
Maier, Claudia S.
DeNoyer, Linda
Beckman, Joseph S.
Publication Title: 
Neurobiology of Disease

NADPH oxidase has recently been identified as a promising new therapeutic target in ALS. Genetic deletion of NADPH oxidase (Nox2) in the transgenic SOD1(G93A) mutant mouse model of ALS was reported to increase survival remarkably by 97 days. Furthermore, apocynin, a widely used inhibitor of NADPH oxidase, was observed to dramatically extend the survival of the SOD1(G93A) ALS mice even longer to 113 days (Harraz et al. J Clin Invest 118: 474, 2008). Diapocynin, the covalent dimer of apocynin, has been reported to be a more potent inhibitor of NADPH oxidase.

Author(s): 
Trumbull, Kari A.
McAllister, Donna
Gandelman, Mandi M.
Fung, Whitney Y.
Lew, Thomas
Brennan, Lucy
Lopez, Nathan
Morré, Jeff
Kalyanaraman, Balaraman
Beckman, Joseph S.
Publication Title: 
Circulation Research

RATIONALE: Hyperamylinemia is common in patients with obesity and insulin resistance, coincides with hyperinsulinemia, and results in amyloid deposition. Amylin amyloids are generally considered a pancreatic disorder in type 2 diabetes. However, elevated circulating levels of amylin may also lead to amylin accumulation and proteotoxicity in peripheral organs, including the heart. OBJECTIVE: To test whether amylin accumulates in the heart of obese and type 2 diabetic patients and to uncover the effects of amylin accumulation on cardiac morphology and function.

Author(s): 
Despa, Sanda
Margulies, Kenneth B.
Chen, Le
Knowlton, Anne A.
Havel, Peter J.
Taegtmeyer, Heinrich
Bers, Donald M.
Despa, Florin
Publication Title: 
Hypertension

Angiotensin II-induced cardiac damage is associated with oxidative stress-dependent mitochondrial dysfunction. Caloric restriction (CR), a dietary regimen that increases mitochondrial activity and cellular stress resistance, could provide protection. We tested that hypothesis in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs). CR (60% of energy intake for 4 weeks) decreased mortality in dTGRs.

Author(s): 
Finckenberg, Piet
Eriksson, Ove
Baumann, Marc
Merasto, Saara
Lalowski, Maciej M.
Levijoki, Jouko
Haasio, Kristiina
Kytö, Ville
Muller, Dominik N.
Luft, Friedrich C.
Oresic, Matej
Mervaala, Eero
Publication Title: 
Age (Dordrecht, Netherlands)

The role of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis in the lifelong caloric restriction (CR)-associated remodeling of white adipose tissue (WAT), adipocyte size, and gene expression profiles was explored in this study. We analyzed the WAT morphology of 6-7-month-old wild-type Wistar rats fed ad libitum (WdAL) or subjected to CR (WdCR), and of heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (TgAL) or subjected to CR (TgCR). Although less effective in TgAL, the adipocyte size was significantly reduced in WdCR compared with WdAL.

Author(s): 
Chujo, Yoshikazu
Fujii, Namiki
Okita, Naoyuki
Konishi, Tomokazu
Narita, Takumi
Yamada, Atsushi
Haruyama, Yushi
Tashiro, Kosuke
Chiba, Takuya
Shimokawa, Isao
Higami, Yoshikazu
Publication Title: 
Anatomical Record (Hoboken, N.J.: 2007)

During traditional acupuncture, fine needles are inserted subcutaneously and rotated, which causes loose fascial tissue to wind around the needle. This coupling is stronger at acupuncture points, which tend to fall above intermuscular fascial planes, than control points, which lay above skeletal muscle. These different anatomical constraints may affect the mechanical coupling. Fascia at acupuncture points is bounded on two sides by skeletal muscle, but at control points is essentially unbounded. These differences were approximated in simple in vitro models.

Author(s): 
Julias, Margaret
Buettner, Helen M.
Shreiber, David I.
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