An unprecedented metal-free regioselective halogenation of 2H-indazoles is reported, and not only realizes the highly selective synthesis of mono-halogenated products, but also complete poly-halogenations.
Age-Related Changes in Protein Oxidation and Proteolysis in Mammalian Cells
作者:T. Grune、R. Shringarpure、N. Sitte、K. Davies
DOI:10.1093/gerona/56.11.b459
日期:2001.11.1
Reactive oxygen species generated as by-products of oxidative metabolism, or from environmental sources, frequently damage cellular macromolecules. Proteins are recognized as major targets of oxidative modification, and the accumulation of oxidized proteins is a characteristic feature of aging cells. An increase in the amount of oxidized proteins has been reported in many experimental aging models, as measured by the level of intracellular protein carbonyls or dityrosine, or by the accumulation of protein-containing pigments such as lipofuscin and ceroid bodies. In younger individuals, moderately oxidized soluble cell proteins appear to be selectively recognized and rapidly degraded by the proteasome. An age-related accumulation of oxidized proteins could, therefore, be a result of declining activity of the proteasome. Previous research to investigate the notion of an age-related decline in the content and/or activity of the proteasome has generated contradictory results. The latest evidence, including our own recent findings, indicates that proteasome activity does, indeed, decline during aging as the enzyme complex is progressively inhibited by oxidized and cross-linked protein aggregates. We propose that cellular aging involves both an increase in (mitochondrial) oxidant production and a progressive decline in proteasome activity. Eventually so much proteasome is inactivated that oxidized proteins begin to accumulate rapidly and contribute to cellular dysfunction and senescence.
ARDAKANI, MANOUCHEHR, AZADI;SMALLEY, R. K.;SMITH, R. H., J. CHEM. SOC. PERKIN TRANS., 1983, N 10, 2501-2506
作者:ARDAKANI, MANOUCHEHR, AZADI、SMALLEY, R. K.、SMITH, R. H.
DOI:——
日期:——
Kenner, Journal of the Chemical Society, 1914, vol. 105, p. 2736
作者:Kenner
DOI:——
日期:——
Ardakani, Manouchehr Azadi; Smalley, Robert K.; Smith, Richard H., Journal of the Chemical Society. Perkin transactions I, 1983, # 10, p. 2501 - 2506
作者:Ardakani, Manouchehr Azadi、Smalley, Robert K.、Smith, Richard H.