![½ðʨ¹ó±ö»á-±öÖÁÈç¹é-×ð¹ó-ÏÔºÕ](/upload/20230419/1guceu8r43a71n4u1r.png)
΢ÐÅɨһɨÁ¬Ã¦×Éѯ
£¨1£© ÍÀë×ÓÔÚϸ°ûÐÄÀíÀú³ÌÖеÄÖ÷Òª×÷ÓÃ
ϸ°ûéæÃüÊÇÒ»ÖÖÕý³£µÄÉúÃüÕ÷Ïó£¬ÆäÏà¹ØÑо¿Ò»Ö±ÊÇÉúÃü¿ÆѧÁìÓòµÄÈÈÃÅ¡£ÓëÌúÏàËÆ£¬ÍÒ²ÊÇËùÓÐÉúÎïÌåÄÚ²»¿Éȱ°±ÉÄÒ»ÖÖ΢Á¿ÔªËØ£¬ÔÚͨÀýµÄ»¯Ñ§·´Ó¦ºÍÐÄÀíÌõ¼þÏ£¬»¹ÔÐÍCu+¿Éת±äΪÑõ»¯ÐÍCu2+¡£ÍÀë×Ó¿ÉÓë¶àÖÖÂÑ°×ÖÊ»òøÍŽᣬ×÷Ϊ¸¨ÖúÒò×Ó»ò½á¹¹×é³É²¿·Ö£¬¼ÓÈëµ÷¿ØÄÜÁ¿´úл¡¢ÏßÁ£ÌåºôÎüºÍ¿¹Ñõ»¯µÈ¶à¸öÐÄÀíÀú³Ì¡£
£¨2£©ÍéæÃü£¨Cuproptosis£©£ºÒ»ÖÖÐÂÐÍÊÜ¿ØÐÔϸ°ûéæÃü»úÖÆ
2022Äê3ÔÂÔÚ¡¶Science¡·ÉϽÒÏþÌâΪCopper induces cell death by targeting lipoylated TCA cycle proteinsµÄÎÄÕÂÖУ¬Ñо¿Ö°Ô±½«Ò»ÖÖ±¬·¢ÆøÖÆÏÔ×ÅÇø±ðÓÚÒÑÖªµÄϸ°ûµòÍö¡¢Ï¸°û½¹Íö¼°ÌúéæÃüµÄÊÜ¿ØÐÔϸ°ûéæÃü·½·¨£¬ÃüÃûΪ¡°ÍéæÃü¡±£¨Cuproptosis£©¡£Ñо¿Ö°Ô±·¢Ã÷ÍéæÃüÒÀÀµÓÚÏßÁ£ÌåºôÎü--ÍÀë×Óͨ¹ýÖ±½ÓÍŽáÈýôÈËáÑ»·Í¾¾¶ÖеÄÁòÐÁõ£»¯ÂÑ°×£¬µ¼ÖÂÁòÐÁõ£»¯ÂÑ°×Ò쳣Ⱥ¼¯£¬²¢×ÌÈźôÎüÁ´¸´ºÏÌåÖеÄÌúÁò´ØÂÑ°×£¬½ø¶øÒý·¢ÂÑ°×Öʶ¾ÐÔÓ¦¼¤£¬×îÖÕÖÂʹϸ°ûéæÃü¡£
£¨3£©10¸öÓëÍéæÃüÏà¹ØµÄ»ùÒò?
?1.ÏßÁ£ÌåºôÎüµ÷ÀíÍÀë×ÓÔØÌåÓÕµ¼µÄϸ°ûéæÃüÑо¿·¢Ã÷£¬ÓÃÍÀë×ÓÔØÌå´¦Öóͷ£²»»áÏÔÖø½µµÍ»ù´¡ºôÎü»òATPÏà¹ØºôÎü£¬µ«»áÏÔÖø½µµÍºôÎüµÄ´¢±¸ÄÜÁ¦£¬ÕâÅúעͲ»Ö±½Ó°ÐÏòETC£¬¶øÊÇ°ÐÏòTCAÑ»·µÄ×é³É²¿·Ö¡£
2.ÍéæÃüµÄÒªº¦µ÷¿Ø»ùÒòFDX1£¬ÊÇÂÑ°×ÖÊÖ¬»¯µÄÉÏÓε÷ÀíÒò×ÓΪÁËÈ·¶¨½éµ¼Í¶¾ÐÔµÄÌض¨´úл;¾¶£¬Ñо¿Õßͨ¹ýCRISPR»ùÒòÇóýɸѡ·¢Ã÷£¬ÇóýFDX1»áÏ÷ÈõÍÀë×ÓÔØÌåÓÕµ¼µÄϸ°ûéæÃü¡£
3.ÍÖ±½ÓÍŽᲢÓÕµ¼Ö¬õ£»¯DLATµÄ¹Ñ¾Û»¯ÂÑ°×ÖʵÄÁòÐÁõ£»¯ÐÞÊÎÊÇÍŽá͵ÄÐëÒªÌõ¼þ¡£ÍÓëÁòÐÁõ£»¯ÂÑ°× DLAT µÄÍŽᣬ»áµ¼ÖÂÂѰ׵ĹѾۻ¯£¬¶ø Elesclomol ´¦Öóͷ£»áÔöÌí DLAT ÂѰ׵ĹѾۻ¯¡£
£¨4£©Í´ß»¯Ñõ»¯Ó¦¼¤
ͽ鵼Fenton·´Ó¦´ß»¯ºÏ³É×î»îÔ¾µÄôÇ»ù×ÔÓÉ»ù£¬´Ó¶øµ¼ÖÂϸ°ûÖеÄROSŨ¶ÈÉý¸ß£¬µ¼ÖÂϸ°ûéæÃü¡£±ðµÄÍ¿ÉÒÔ½«»¹ÔµÄ¹Èë׸ÊëÄÑõ»¯³ÉÑõ»¯Ð͹Èë׸ÊëĶþÁòÎoxidizedglutathionedisulfide£¬GSSG£©£¬µ¼Ö¿¹Ñõ»¯¼Á¹Èë׸ÊëĵĺĽߣ¬´Ó¶ø×ÌÈŹÈë׸ÊëÄÏà¹ØµÄ¿¹Ñõ»¯·ÀÓùϵͳ£¬Óɴ˵¼ÖÂϸ°ûéæÃü¡£
Ñо¿Åú×¢ÍòüºÏ¼ÁÒÁÀû˾Ī£¨Elesclomol£¬ES£©£¬Ò»Öָ߶ÈÇ×Ö¬ÐÔµÄÍÍŽá·Ö×Ó£¬Ëü¿ÉÒÔòüºÏϸ°ûÍâµÄCu2+£¬ÐγÉÒ»ÖÖÒÔES-Cu2+¸´ºÏÎïµÄÐÎʽ£¬½«ÍÔËË͵½ÏßÁ£ÌåÖб¬·¢Ñõ»¯Ó¦¼¤´Ó¶ø´¥·¢Ï¸°ûµòÍö¡£
?£¨5£©ÍéæÃüÔÚÖ×ÁöÖеÄÏà¹ØÑо¿
ÍÀë×ӵĺ¬Á¿Î¬³Ö¶¯Ì¬Æ½ºâ£¬Ê§ºâ¿Éµ¼ÖÂÑõ»¯Ó¦¼¤ºÍϸ°û×ÔÊÉÒì³£µÈ£¬´Ó¶øÓÕ·¢¶àÖÖÍ»òÍÀë×ÓÏà¹ØÐÔ¼²²¡µÄ±¬·¢¡£
ÈéÏÙ°© ÓÐÑо¿Åú×¢ÈéÏÙ°©»¼ÕßѪÇåÖÐCu2+º¬Á¿¸ßÓÚÕý·²ÈË¡£ÈéÏÙ°©ÏßÁ£ÌåÖÐÍÅóÙÂÑ°×COX17ºÍSCO2±í´ïÉϵ÷£¬Õâ˵Ã÷ÈéÏÙ°©Ï¸°û±ÈÕý³£Ï¸°û¶ÔÍÏòÏßÁ£ÌåÔËÊäµÄÐèÇó¸ü¸ß¡£
½áÖ±³¦°© ÍÓëÖ×Áö΢ÇéÐÎÖеÄÑ×Ö¢Òò×ÓÏ໥×÷Óã¬Ñ×Ö¢Òò×ÓIL-17ͨ¹ýÓÕµ¼STEAP4À´Íƶ¯Ï¸°û¶Ô͵ÄÉãÈ¡£¬´Ó¶øÔö½øÁËÈ´Ö±³¦°©µÄ±¬·¢¡£Òò´Ëϸ°ûÍ´úл״̬¿ÉÄÜÊÇ°©Ï¸°û¶ÔIL-17´Ì¼¤·´Ó¦µÄÒªº¦ÒòËØ¡£
·Î°© ÓÐÑо¿Åú×¢ÐÄÀíŨ¶ÈµÄCu2+ÍŽáDisulfiram¶Ô·ÇСϸ°û·Î°©Ï¸°ûÓÐÑ¡Ôñ¶¾ÐÔ¡£
²Î¿¼ÎÄÏ×£º
[1] Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022;375(6586):1254-1261.
¹Øע΢ÐŹ«ÖÚºÅ
΢ÐÅɨһɨÁ¬Ã¦×Éѯ
΢ÐÅɨһɨÁ¬Ã¦×Éѯ