Oxidation of KCNB1 K~+ channels in central nervous system and beyond

• 作者: Federico Sesti Shuang Liu Xilong Wu
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: Apoptosis Kv2.1 Aging REACTIVE oxygen species Alzheimer’s disease
• 年，卷（期）: 2014,（2）
• 页码范围: 85-92
• 页数: 8页
• 分类号: R749.16

摘要

KCNB1, a voltage-gated potassium(K+) channel that conducts a major delayed rectifier current in the brain, pancreas and cardiovascular system is a key player in apoptotic programs associated with oxidative stress. As a result, this protein represents a bona fide drug target for limiting the toxic effects of oxygen radicals. Until recently the consensus view was that reactive oxygen species trigger a pro-apoptotic surge in KCNB1 current via phosphorylation and SNARE-dependent incorpora-tion of KCNB1 channels into the plasma membrane. However, new evidence shows that KCNB1 can be modified by oxidants and that oxidized KCNB1 channels can directly activate pro-apoptotic signaling pathways. Hence, a more articulated picture of the pro-apoptotic role of KCNB1 is emerging in which the protein induces cell’s death through distinct molecular mechanisms and activation of multiple pathways. In this review article we discuss the diverse functional, toxic and protective roles that KCNB1 channels play in the major organs where they are expressed.