Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation.

摘要: Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has central role in HHcy-induced cellular injury the brain. We observed accumulation LC3B-II p62 was associated with increased MTOR signaling human primary astrocyte cultures as well diet-induced model HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), protease cathepsin D, suggesting dysfunction also contributed to autophagic defect. Moreover, unfolded response. Interestingly, Vitamin B supplementation restored flux, alleviated ER stress, reversed due HHCy. Furthermore, inducer, rapamycin able relieve stress reverse caused by vitro. Inhibition exacerbated during oxygen glucose deprivation reperfusion (OGD/R), oxidative stress. These effects were prevented co-treatment, it may be helpful relieving detrimental ischemia/reperfusion or Collectively, these findings show therapy can defects HHcy; thus potential treatment reduce ischemic damage stroke patients HHcy.