Stem-cell approaches for kidney repair: choosing the right cells

With the increasing rate of end-stage renal failure and limited alternatives for its treatment, stem cell (SC) therapy for kidney injury is urgently needed. Choosing the right SC type is the critical step in realizing the potential of this therapeutic approach. Four possible sources of SCs are envisioned for the development of this type of treatment: (i) bone-marrow-derived SCs (BMSCs), (ii) renal adult SCs, (iii) embryonic SCs and (iv) fetal renal SCs. We suggest that resident SCs recently identified in the Bowman's capsule of adult human kidneys might prospectively be the ideal cell type for treatment of both acute and chronic renal injury because they display the potential to differentiate into multiple types of renal cells. However, BMSCs also represent an attractive alternative, especially for the treatment of patients affected by acute renal failure.     

Fluorescence and photochemical properties of phytochromes in wild-type wheat and a transgenic line overexpressing an oat phytochrome A (PHYA) gene: functional implications

Etiolated seedlings of wild‐type wheat and a transgenic line overexpressing an oat PHYA gene were investigated by the use of in situ low‐temperature fluorescence spectroscopy. The red‐absorbing phytochrome form, Pr, was characterized by (1) fluorescence emission spectrum; (2) total phytochrome content, and (3) by the extent of the Pr → lumi‐R photoconversion at low temperature (γ₁), and of the Pr → Pfr photoconversion at ambient temperature (γ₂) as derived from emission data. All the characteristics were shown to be variable and to depend on (1) organ and tissue used; (2) seedling age; (3) transgenic wheat modification, and (4) continuous far‐red irradiation of seedlings during their growth. These variations were interpreted in terms of the existence in wheat seedlings of the two phenomenological Pr types: (a), Pr′– major longer wavelength (687/673 nm, emission/absorption maxima) variable and light‐labile with γ₁ ≈ 0·5; and (b), Pr′′– minor, shorter wavelength (682/668 nm), relatively constant with its concentration not changing significantly with the increase of total phytochrome content in tissues and light‐stable with γ₁ ≤ 0·05–0·1. Overexpression of oat phyA increases primarily the content of Pr′ suggesting that it is comprised of phyA (phyA′) whereas Pr′′ is believed to consist of the minor phyA fraction (phyA′′) and phyB. The transgenic wheat line has been demonstrated to have a modified phenotype – the appearance of the far‐red high irradiance reaction (FR‐HIR) (Shlumukov et al. Plant, Cell and Environment 24, 703–712). The increased content of phyA′ in the transgenic line, whereas the total [phyA′′ + phyB] remains the same as in the wild type, indicates that the phyA′ pool is primarily responsible for the observed modification of the phenotype and suggests that even in wild‐type plants the phyA′ component of the phyA pool may mediate the FR‐HIR.     

Methamphetamine produces neuronal inclusions in the nigrostriatal system and in PC12 cells

Mice treated with the psychostimulant methamphetamine (MA) showed the appearance of intracellular inclusions in the nucleus of medium sized striatal neurones and cytoplasm of neurones of the substantia nigra pars compacta but not in the frontal cortex. All inclusions contained ubiquitin, the ubiquitin activating enzyme (E1), the ubiquitin protein ligase (E3-like, parkin), low and high molecular weight heat shock proteins (HSP 40 and HSP 70). Inclusions found in nigral neurones stained for alpha-synuclein, a proteic hallmark of Lewy bodies that are frequently observed in Parkinson's disease and other degenerative disorders. However, differing from classic Lewy bodies, MA-induced neuronal inclusions appeared as multilamellar bodies resembling autophagic granules. Methamphetamine reproduced this effect in cultured PC12 cells, which offered the advantage of a simple cellular model for the study of the molecular determinants of neuronal inclusions. PC12 inclusions, similar to those observed in nigral neurones, were exclusively localized in the cytoplasm and stained for alpha-synuclein. Time-dependent experiments showed that inclusions underwent a progressive fusion of the external membranes and developed an electrodense core. Inhibition of dopamine synthesis by alpha-methyl-p-tyrosine (alphaMpT), or administering the antioxidant S-apomorphine largely attenuated the formation of inclusions in PC12 cells exposed to MA. Inclusions were again observed when alphaMpT-treated cells were loaded with l-DOPA, which restored intracellular dopamine levels.