Matrix imbalance by inducing expression of metalloproteinase and oxidative stress in cochlea of hyperhomocysteinemic mice

Kundu, Soumi; Tyagi, Neetu; Sen, Utpal; Tyagi, Suresh C.

doi:10.1007/s11010-009-0194-2

Cited by 30 publications

(22 citation statements)

References 38 publications

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“…We have recently reported increased placental levels of MMP1 (collagenase) and MMP9 (gelatinase) in women delivering preterm (Sundrani et al 2012). The activity of MMPs is reported to be regulated by homocysteine, oxidative stress, and long-chain polyunsaturated fatty acids (LCPUFA; Guo et al 2006, Kundu et al 2009, Solakivi et al 2009, Zainal et al 2009, Zeydanli & Turan 2009, Ke et al 2010.…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

Sundrani¹,

Chavan‐Gautam²,

Pisal³

et al. 2013

Reproduction

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Maternal nutrition is an important determinant of one-carbon metabolism and defects in the one-carbon metabolism may lead to poor obstetric outcomes. This study was designed to test the hypothesis that altered intake/metabolism of micronutrients (folic acid and vitamin B 12 ) and docosahexaenoic acid (DHA) contributes to increased homocysteine and oxidative stress leading to altered levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in women delivering preterm. We have earlier reported increased vitamin B 12 , homocysteine, and oxidative stress along with reduced placental DHA in women delivering preterm. In this study, we further examine the placental levels of MMP2, MMP3, TIMP1, and TIMP2 in 75 women delivering at term and 73 women delivering preterm. Placental levels of MMPs and TIMPs were determined by ELISA. Placental MMP2 and MMP3 levels were higher (P!0.01) in women delivering preterm as compared with term. There was no difference in the placental TIMP1 and TIMP2 levels in women delivering preterm and at term. Further placental MMP2 and MMP3 levels were higher (P!0.01) in women with preterm labor as compared with those in labor at term, suggesting that MMPs may favor degradation of extracellular matrix in the placenta during preterm labor. Our study for the first time suggests a crucial role of micronutrients and MMPs in preterm birth. Future studies need to examine if epigenetic modifications through the one-carbon cycle contribute to increased levels of MMPs leading to preterm deliveries.

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Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

Sundrani¹,

Chavan‐Gautam²,

Pisal³

et al. 2013

Reproduction

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“…The maintenance of ECM homeostasis has been shown to be important for inner ear development (Szabova et al; Davies et al, 2007), and the dysregulation of this structure leads to sensorineural hearing loss (Gratton et al, 2005; Kundu et al, 2009; Nam et al, 2011; Setz et al, 2011). In noise-traumatized cochleae, morphological changes in ECM structures have been documented (Canlon, 1987, 1988).…”

Section: Introductionmentioning

confidence: 99%

Metalloproteinases and Their Associated Genes Contribute to the Functional Integrity and Noise-Induced Damage in the Cochlear Sensory Epithelium

Cai

et al. 2012

J. Neurosci.

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Matrix metalloproteinases (MMPs) and their related gene products regulate essential cellular functions. An imbalance in MMPs has been implicated in various neurological disorders, including traumatic injuries. Here, we report a role for MMPs and their related gene products in the modulation of cochlear responses to acoustic trauma in rats. The normal cochlea was shown to be enriched in MMP enzymatic activity, and this activity was reduced in a time-dependent fashion after traumatic noise injury. The analysis of gene expression by RNA-seq and qRT-PCR revealed the differential expression of MMPs and their related genes between functionally specialized regions of the sensory epithelium. The expression of these genes was dynamically regulated between the acute and chronic phases of noise-induced hearing loss. Moreover, noise-induced expression changes in two endogenous MMP inhibitors, Timp1 and Timp2, in sensory cells were dependent upon the stage of nuclear condensation, suggesting a specific role for MMP activity in sensory cell apoptosis. A short-term application of doxycycline, a broad-spectrum inhibitor of MMPs, prior to noise exposure reduced noise-induced hearing loss and sensory cell death. By contrast, a 7-day treatment compromised hearing sensitivity and potentiated noise-induced hearing loss. This detrimental effect of the long-term inhibition of MMPs on noise-induced hearing loss was further confirmed using targeted Mmp7 knockout mice. Together, these observations suggest that MMPs and their related genes participate in the regulation of cochlear responses to acoustic overstimulation and that the modulation of MMP activity can serve as a novel therapeutic target for the reduction of noise-induced cochlear damage.

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“…It is known that acute hearing loss as well as age-related hearing loss can be a sequel of altered blood flow to the inner ear, specifically the cochlea. They postulated that HHCY may affect the cochlear microcirculation in the same way as it does the BBB [18].…”

Section: Homocysteine the Cochlea And Hearingmentioning

confidence: 99%

Hyperhomocysteinemia, MMPs and Cochlear Function: A Short Review

Bhargava

et al. 2015

Ind J Clin Biochem

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Hyperhomocysteinemia (HHCY) has been demonstrated to affect cochlear microvasculature as well as cochlear epithelial cells directly, with a resultant alteration of the expression of matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Hence, ascertaining the optimum concentration of MMPs and TIMPs in the cochlea could help to inhibit hearing loss due to HHCY by the administration of appropriate MMP inhibitors, Since infections/inflammations as well as ototoxic antibiotics have a similar mechanism of otic pathology, the cochlear damage they cause could also be similarly prevented.

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Matrix imbalance by inducing expression of metalloproteinase and oxidative stress in cochlea of hyperhomocysteinemic mice

Cited by 30 publications

References 38 publications

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

Metalloproteinases and Their Associated Genes Contribute to the Functional Integrity and Noise-Induced Damage in the Cochlear Sensory Epithelium

Hyperhomocysteinemia, MMPs and Cochlear Function: A Short Review

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