The potential effect of type 2 diabetes mellitus on lumbar disc degeneration: a retrospective single-center study

Abstract Background Diabetes mellitus (DM) and low back pain which is mainly caused by degeneration of the intervertebral discs (IVDs) both are major public health problem worldwide. The present study was designed to investigate the association between type 2 diabetes mellitus (T2D) and severity of lumbar disc degeneration (LDD). Methods We retrospectively reviewed patients with low back pain visiting our spine clinic in 2014. Low back pain patients all have the lumbar MRI imaging and no previous treatment. One hundred fifty patients without T2D (group A) and 622 patients with T2D meeting the criteria were included. Sex, age, body mass index (BMI), high blood pressure (HBP), history of smoking, alcohol use, and duration of T2D were recorded. Patients with T2D were assigned to a well-controlled group (group B, n = 380) and a bad-controlled group (group C, n = 242). In group B, T2D duration of 148 patients was ≤ 10 years (group B1) and 232 patients > 10 years (group B2). In group C, T2D duration of 100 patients was ≤ 10 years (group C1) and 142 patients > 10 years (group C2). The severity of LDD was evaluated using the five-level Pfirrmann grading system. Data were analyzed using SPSS 19.0. Results Demographic data except age showed no difference among groups (P > 0.5). Compared to patients without T2D, patients with T2D showed more severe disc degeneration after removal of age effects (P  0.05); groups B2, C1, and C2 showed higher average Pfirrmann scores than group A (P  10 years and a bad control of T2D were risk factors for LDD. The longer T2D duration was, the more severe disc degeneration would be

The Actin-Related Protein2/3 Complex Regulates Mitochondrial-Associated Calcium Signaling during Salt Stress in Arabidopsis

Microfilament and Ca2+ dynamics play important roles in stress signaling in plants. Through genetic screening of Arabidopsis thaliana mutants that are defective in stress-induced increases in cytosolic Ca2+ ([Ca2+] (cyt)), we identified Actin-Related Protein2 (Arp2) as a regulator of [Ca2+] cyt in response to salt stress. Plants lacking Arp2 or other proteins in the Arp2/3 complex exhibited enhanced salt-induced increases in [Ca2+] cyt, decreased mitochondria movement, and hypersensitivity to salt. In addition, mitochondria aggregated, the mitochondrial permeability transition pore opened, and mitochondrial membrane potential psi m was impaired in the arp2 mutant, and these changes were associated with salt-induced cell death. When opening of the enhanced mitochondrial permeability transition pore was blocked or increases in [Ca2+] cyt were prevented, the salt-sensitive phenotype of the arp2 mutant was partially rescued. These results indicate that the Arp2/3 complex regulates mitochondrial-dependent Ca2+ signaling in response to salt stress

GSK3-like kinases positively modulate abscisic acid signaling through phosphorylating subgroup III SnRK2s in Arabidopsis

Arabidopsis glycogen synthase kinase 3 (GSK3)-like kinases have versatile functions in plant development and in responding to abiotic stresses. Although physiological evidence suggested a potential role of GSK3-like kinases in abscisic acid (ABA) signaling, the underlying molecular mechanism was largely unknown. Here we identified members of Snf1-related kinase 2s (SnRK2s), SnRK2.2 and SnRK2.3, that can interact with and be phosphorylated by a GSK3-like kinase, brassinosteroid insensitive 2 (BIN2). bin2-3 bil1 bil2, a loss-of-function mutant of BIN2 and its two closest homologs, BIN2 like 1 (BIL1) and BIN2 like 2 (BIL2), was hyposensitive to ABA in primary root inhibition, ABA-responsive gene expression, and phosphorylating ABA Response Element Binding Factor (ABF) 2 fragment by in-gel kinase assays, whereas bin2-1, a gain-of-function mutation of BIN2, was hypersensitive to ABA, suggesting that these GSK3-like kinases function as positive regulators in ABA signaling. Furthermore, BIN2 phosphorylated SnRK2.3 on T180, and SnRK2.3(T180A) had decreased kinase activity in both autophosphorylation and phosphorylating ABFs. Bikinin, a GSK3 kinase inhibitor, inhibited the SnRK2.3 kinase activity and its T180 phosphorylation in vivo. Our genetic analysis further demonstrated that BIN2 regulates ABA signaling downstream of the PYRABACTIN RESISTANCE1/PYR1-LIKE/REGULATORY COMPONENTS OF ABA RECEPTORS receptors and clade A protein phosphatase 2C but relies on SnRK2.2 and SnRK2.3. These findings provide significant insight into the modulation of ABA signaling by Arabidopsis GSK3-like kinases

GSK3-like kinases positively modulate abscisic acid signaling through phosphorylating subgroup III SnRK2s in Arabidopsis

Arabidopsis glycogen synthase kinase 3 (GSK3)-like kinases have versatile functions in plant development and in responding to abiotic stresses. Although physiological evidence suggested a potential role of GSK3-like kinases in abscisic acid (ABA) signaling, the underlying molecular mechanism was largely unknown. Here we identified members of Snf1-related kinase 2s (SnRK2s), SnRK2.2 and SnRK2.3, that can interact with and be phosphorylated by a GSK3-like kinase, brassinosteroid insensitive 2 (BIN2). bin2-3 bil1 bil2, a loss-offunction mutant of BIN2 and its two closest homologs, BIN2 like 1 (BIL1) and BIN2 like 2 (BIL2), was hyposensitive to ABA in primary root inhibition, ABA-responsive gene expression, and phosphorylating ABA Response Element Binding Factor (ABF) 2 fragment by in-gel kinase assays, whereas bin2-1, a gain-of-function mutation of BIN2, was hypersensitive to ABA, suggesting that these GSK3-like kinases function as positive regulators in ABA signaling. Furthermore, BIN2 phosphorylated SnRK2.3 on T180, and SnRK2.3T180A had decreased kinase activity in both autophosphorylation and phosphorylating ABFs. Bikinin, a GSK3 kinase inhibitor, inhibited the SnRK2.3 kinase activity and its T180 phosphorylation in vivo. Our genetic analysis further demonstrated that BIN2 regulates ABA signaling downstream of the PYRABACTIN RESISTANCE1/PYR1-LIKE/REGULATORY COMPONENTS OF ABA RECEPTORS receptors and clade A protein phosphatase 2C but relies on SnRK2.2 and SnRK2.3. These findings provide significant insight into the modulation of ABA signaling by Arabidopsis GSK3-like kinases