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Tibialis anterior muscles of 45-week-old female obese Zucker rats with defective leptin receptor and non-insulin dependent diabetes mellitus (NIDDM) showed a significative atrophy compared to lean muscles, based on histochemical-stained section’s measurements in the sequence: oxidative slow twitch (SO, type I) < oxidative fast twitch (FOG, type IIa) < fast glycolytic (FG, type IIb). Both oxidative fiber’s outskirts resembled ‘ragged’ fibers and, in these zones, ultrastructure revealed small clusters of endoplasm-like reticulum filled with unidentified electron contrasted compounds, contiguous and continuous with adjacent mitochondria envelope. The linings appeared crenated stabbed by circular patterns resembling those found of ceramides. The same fibers contained scattered degraded mitochondria that tethered electron contrasted droplets favoring larger depots while mitoptosis were widespread in FG fibers. Based on other interdisciplinary investigations on the lipid depots of diabetes 2 muscles made us to propose these accumulated contrasted contents to be made of peculiar lipids, including acyl-ceramides, as those were only found while diabetes 2 progresses in aging obese rats. These could interfere in NIDDM with mitochondrial oxidative energetic demands and muscle functions.

ABCB5 is a member of the ABC transporter superfamily composed of 48 transporters, which have been extensively studied for their role in cancer multidrug resistance and, more recently, in tumorigenesis. ABCB5 has been identified as a marker of skin progenitor cells, melanoma, and limbal stem cells. It has also been associated with multidrug resistance in several cancers. The unique feature of ABCB5 is that it exists as both a full transporter (ABCB5FL) and a half transporter (ABCB5β). Several studies have shown that the ABCB5β homodimer does not confer multidrug resistance, in contrast to ABCB5FL. In this study, using three complementary techniques; (1) nanoluciferase-based bioluminescence resonance energy transfer, (2) co-immunoprecipitation, and (3) proximity ligation assay, we identified two novel heterodimers in melanoma: ABCB5β/B6 and ABCB5β/B9. Both heterodimers could be expressed in high-five insect cells and ATPase assays revealed that they have a basal ATPase activity. These results are an important step toward untangling the functional role of ABCB5β in melanocytes and melanoma.

xCT protein is the specific subunit of System xc-, a multi-proteic complex importing cystine into cell while releasing extracellular glutamate. Although xCT protein expression is detected in brain glial cells, its expression in the spinal cord and during spinal cord disorders remain elusive. The aim of this study is to characterize the contribution of xCT to functional and histological outcomes following SCI, using wild-type mice (xCT+/+) and genetically-invalidated mice (xCT-/-). In situ hybridization allowed to detect xCT mRNA mostly in astrocyte subpopulations and in meningeal fibroblasts in the normal spinal cord. During the subacute phase of spinal cord injury, xCT mRNA could also be detected in significant amount in microglial cells. Moreover, overall xCT mRNA levels were upregulated, peaking at 4 days post-injury. While both injured xCT+/+ and xCT-/- mice recovered partly their motor functions, xCT-/- mice recovered muscular grip strength as well as pre-SCI weight substantially faster than xCT+/+ mice.Histology of injured spinal cords revealed increased number of motor neurons in xCT-/- mice at multiple distances around lesion epicenter. Intraspinal glutathione levels were unchanged in both injured groups. As xCT has been demonstrated as a regulator of microglial function (Mesci et al., Brain, 2015), we assessed markers of microglial activation. At 2 weeks post-SCI, the number of type A Iba1+ cells was unexpectedly much higher in contused xCT-/- than in xCT+/+ spinal cords. Analysis of M1/M2 polarization showed that contused xCT-/- spinal cords contained higher mRNA levels of Ym1 and IGF-1 (M2) while lower levels of NOX2 and TNF-a (M1). Additionally, the number of reactive astrocytes was slightly higher in xCT-/- mice. The number of surviving oligodendrocytes was unchanged between the two injured groups. This study suggests that, following SCI trauma, an early xCT upregulation (if confirmed at the protein level) is detrimental to motor neuron survival and influences inflammation by dysbalancing M1/M2 polarization.

xCT protein is the specific subunit of System xc-, a multi-proteic complex importing cystine into cell while releasing extracellular glutamate. Although xCT protein expression is detected in brain glial cells, its expression in the spinal cord and during spinal cord disorders remain elusive. The aim of this study is to characterize the contribution of xCT to functional and histological outcomes following SCI, using wild-type mice (xCT+/+) and genetically-invalidated mice (xCT-/-). In situ hybridization allowed to detect xCT mRNA in astrocyte subpopulations and in meningeal fibroblasts in the normal spinal cord. During the early phase of spinal cord injury, xCT mRNA could also be detected in microglial cells and overall mRNA levels were upregulated, peaking at 4 days post-injury. While both injured xCT+/+ and xCT-/- mice recovered partly their motor functions, xCT-/- mice recovered muscular grip strength as well as pre-SCI weight substantially faster than xCT+/+ mice. Histology of injured spinal cords revealedincreased number of motor neurons in xCT-/- mice at multiple distances around lesion epicenter. As xCT has been demonstrated as a regulator of microglial function (Mesci et al., Brain, 2015), we assessed markers of microglial activation. At 2 weeks post-SCI, the number of type A Iba1+ cells was unexpectedly much higher in contused xCT-/- than in xCT+/+ spinal cords. Analysis of M1/M2 polarization showed that contused xCT-/- spinal cords contained higher mRNA levels of Ym1 and IGF-1 (M2) while lower levels of NOX2 and TNF-a (M1). Additionally, the number of astrocytes and oligodendrocytes were unchanged between the two injured groups. This study suggests that, following SCI trauma, an early xCT upregulation (if confirmed at the protein level) exacerbates microglia-driven inflammation and influences motor neuron survival.