Protective effects of glutamine on human melanocyte oxidative stress model.

BACKGROUND: Vitiligo is a disorder caused by the loss of the melanocyte activity on melanin pigment generation. Studies show that oxidative-stress induced apoptosis in melanocytes is closely related to the pathogenesis of vitiligo. Glutamine is a well known antioxidant with anti-apoptotic effects, and is used in a variety of diseases. However, it is unclear whether glutamine has an antioxidant or anti-apoptotic effect on melanocytes. AIMS: The aim of this study was to investigate the protective effects of glutamine on a human melanocyte oxidative stress model. METHODS: The oxidative stress model was established on human melanocytes using hydrogen peroxide. The morphology and viability of melanocytes, levels of oxidants [reactive oxygen species and malondialdehyde], levels of antioxidants [superoxide dismutase and glutathione-S-transferase], and apoptosis-related indicators (caspase-3, bax and bcl-2) were examined after glutamine exposure at various concentrations. Expressions of nuclear factor-E2-related factor 2, heme oxygenase-1, and heat shock protein 70 were detected using western blot technique after glutamine exposure at various concentrations. RESULTS: Our results demonstrate that pre-treatment and post-treatment with glutamine promoted melanocyte viability, increased levels of superoxide dismutase, glutathione-S-transferase and bcl-2, decreased levels of reactive oxygen species, malondialdehyde, bax and caspase-3, and enhanced nuclear factor-E2-related factor 2, heme oxygenase-1, and heat shock protein 70 expression in a dose dependent manner. The effect of pre-treatment was more significant than post-treatment, at the same concentration. LIMITATIONS: The mechanisms of glutamine activated nuclear factor-E2-related factor 2 antioxidant responsive element signaling pathway need further investigation. CONCLUSIONS: Glutamine enhances the antioxidant and anti-apoptotic capabilities of melanocytes and protects them against oxidative stress.

Mycobacterium leprae induces insulin-like growth factor and promotes survival of Schwann cells upon serum withdrawal.

Peripheral nerve lesions are considered the most relevant symptoms of leprosy, a chronic infectious disease caused by Mycobacterium leprae. The strategies employed by M. leprae to infect and multiply inside Schwann cells (SCs), however, remain poorly understood. In this study, it is shown that treatment of SCs with M. leprae significantly decreased cell death induced by serum deprivation. Not displayed by Mycobacterium smegmatis or Mycobacterium bovis BCG, the M. leprae survival effect was both dose dependent and specific. The conditioned medium (CM) of M. leprae-treated cultures was seen to mimic the protective effect of the bacteria, suggesting that soluble factors secreted by SCs in response to M. leprae were involved in cell survival. Indeed, by quantitative RT-PCR and dot blot/ELISA, it was demonstrated that M. leprae induced the expression and secretion of the SC survival factor insulin-like growth factor-I. Finally, the involvement of this hormone in M. leprae-induced SC survival was confirmed in experiments with neutralizing antibodies. Taken together, the results of this study delineate an important strategy for the successful colonization of M. leprae in the nerve based on the survival maintenance of the host cell through induction of IGF-I production.

Introduction to the review series Autophagy in Higher Eukaryotes--a matter of survival or death.

Single celled eukaryotes utilize autophagy (or self-consumption) to adapt to fluctuating energy sources in the environment. The identification in multicellular organisms of orthologs of autophagy-related yeast genes has led to some of the major advances in the molecular dissection of the pathway in the last decade. In higher eukaryotes, autophagy is much more than a 'stress response' pathway. The complexity of multicellular systems calls for greater sophistication and coordination not only in regulating the stress response but also in sustaining normal physiological functions and a homeostatic environment in the whole organism. The review series on 'Autophagy in Higher Eukaryotes--a matter of survival or death' in the current issue comprises a variety of perspectives on the role of autophagy in cell growth, survival and death, in neurodegeneration, tumor suppression and tumor progression. For example, Høyer-Hansen and Jäättellä cogitate on the emergence of autophagy as a target in cancer therapy. In addition, Sanjuan and Green examine its role in the defense against microbial pathogens and Sachdeva and Thompson offer an intriguing look at autophagy in the context of circadian clocks and diurnal rhythms. Presented below are some of the salient points from these perspectives.

AIF: a multifunctional cog in the life and death machine.

Mitochondria have a dual role in cellular life and death as life-promoting energy providers and as contributors to programmed cell death (apoptosis). The precise sequence of events resulting in the permeabilization of the mitochondrial membrane and the release of mitochondrial resident proteins remains an actively explored topic. Hansen and Nagley describe results from mammalian cells and from the nematode C. elegans that lead to a feedforward model for mitochondrial destabilization. Furthermore, they describe the mitochondrial and apoptotic functions of several proteins released from mitochondria during progression toward cell death.