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Neuropathic pain is a refractory disease characterized by maladaptive changes in gene transcription and translation in the sensory pathway. Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the development of neuropathic pain is unclear. Here we identify a conserved lncRNA, named Kcna2 antisense RNA,(More)
BACKGROUND Homocysteine is known to be an independent risk factor for congenital heart disease (CHD). Methionine synthase reductase (MTRR) is essential for the adequate remethylation of homocysteine, which is the dominant pathway for homocysteine removal during early embryonic development. METHODS AND RESULTS Here, we report that the c.56+781 A>C(More)
AIMS Elevated homocysteine levels are known to be a risk factor for congenital heart disease (CHD), but the mechanism underlying this effect is unknown. During early embryonic development, homocysteine removal is dictated exclusively by the MTR activity. To examine the role of MTR in CHD risk, we identified genetic variants in MTR and investigated the(More)
The development of opioid-induced analgesic tolerance and hyperalgesia is a clinical challenge for managing chronic pain. Adaptive changes in protein translation in the nervous system are thought to promote opioid tolerance and hyperalgesia; however, how opioids drive such changes remains elusive. Here, we report that mammalian target of rapamycin (mTOR),(More)
Homocysteine is an independent risk factor for various cardiovascular diseases. There are two ways to remove homocysteine from embryonic cardiac cells: remethylation to form methionine or transsulfuration to form cysteine. Cystathionine β-synthase (CBS) catalyzes the first step of homocysteine transsulfuration as a rate-limiting enzyme. In this study, we(More)
Voltage-gated potassium (Kv) channels are critical in controlling neuronal excitability and are involved in the induction of neuropathic pain. Therefore, Kv channels might be potential targets for prevention and/or treatment of this disorder. We reported here that a majority of dorsal root ganglion (DRG) neurons were positive for Kv channel alpha subunit(More)
As a well-known transcription factor, TBX5 is involved in embryonic cardiac development. Although TBX5 functions in a dose-dependent manner, the posttranscriptional regulation of human TBX5 is poorly understood. Thus, this study aimed to identify microRNAs that modulate TBX5 expression. Luciferase assays were used to screen miRNAs predicted to modulate TBX5(More)
Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of(More)
In cancer cells, the mammalian target of rapamycin complex 1 (mTORC1) that requires hormonal and nutrient signals for its activation, is constitutively activated. We found that overexpression of pyruvate kinase M2 (PKM2) activates mTORC1 signaling through phosphorylating mTORC1 inhibitor AKT1 substrate 1 (AKT1S1). An unbiased quantitative phosphoproteomic(More)
Nerve injury-induced downregulation of voltage-gated potassium channel subunit Kcna2 in the dorsal root ganglion (DRG) is critical for DRG neuronal excitability and neuropathic pain genesis. However, how nerve injury causes this downregulation is still elusive. Euchromatic histone-lysine N-methyltransferase 2, also known as G9a, methylates histone H3 on(More)